RESUMEN
Estrogens reduce 0.3 M NaCl intake and palatability in a widely used model of essential hypertension, the spontaneously hypertensive rats (SHRs). Here we investigated whether the inhibitory effects of ß-estradiol (E2, 10 µg/kg b.w. subcutaneously for 8 days) on water deprived partially-rehydrated (WD-PR) ovariectomized (OVX) adult female SHRs (fSHRs, n = 4-10/group) are related to interferences on brain angiotensin II AT1 receptors (AT1r). After WD-PR, E2 reduced 0.3 M NaCl intake (1.3 ± 0.6, vs. vehicle: 3.5 ± 1.2 ml/30 min), the number of hedonic responses to intraoral NaCl infusion (57 ± 11, vs. vehicle: 176 ± 32/min), and the relative angiotensin AT1r (Agtr1a) mRNA expression in the hypothalamus. Losartan (AT1r antagonist, 100 µg) intracerebroventricularly in OVX fSHRs treated with vehicle subcutaneously abolished 0.3 M NaCl intake (0.1 ± 0.1 ml/30 min) and only transiently reduced hedonic responses to intraoral NaCl. Losartan combined with E2 decreased the number of hedonic and increased the number of aversive responses to intraoral NaCl and abolished 0.3 M NaCl intake. E2 also reduced the pressor and dipsogenic responses to intracerebroventricular angiotensin II. The results suggest that AT1r activation increases palatability and induces NaCl intake in WD-PR fSHRs. E2 reduced hypothalamic Agtr1a mRNA expression, which may account for the effects of E2 on NaCl intake and palatability and intracerebroventricular angiotensin II-induced pressor and dipsogenic responses in OVX fSHRs. Future studies considering natural fluctuations in estrogen secretion might help to determine the degree of such interference in brain neuronal activity.
Asunto(s)
Angiotensina II , Losartán , Angiotensina II/farmacología , Animales , Estradiol/farmacología , Femenino , Humanos , Losartán/farmacología , ARN Mensajero , Ratas , Ratas Endogámicas SHR , Receptor de Angiotensina Tipo 1/genética , Cloruro de SodioRESUMEN
Spontaneously hypertensive rats (SHRs) ingest more NaCl than normotensive strains. Here we investigated NaCl intake and taste reactivity in adult male SHRs and normotensive Holtzman rats treated or not with AT1 receptor antagonist centrally in euhydrated condition and after fluid depletion. Taste reactivity was measured by the number of orofacial expressions to intra-oral infusions of 0.3 M NaCl. In euhydrated condition, intra-oral infusions of 0.3 M NaCl produced greater number of hedonic responses in SHRs than in normotensive rats, without differences in the number of aversive responses. Compared to euhydrated condition, the treatment with the diuretic furosemide + low dose of captopril (angiotensin converting enzyme blocker) increased the number of hedonic and reduced the number of aversive responses to intra-oral NaCl in normotensive rats, without changing the number of hedonic or aversive responses in SHRs. Losartan (AT1 receptor antagonist, 100 ng/1 µl) injected intracerebroventricularly in SHRs abolished 0.3 M NaCl intake induced by water deprivation + partial rehydration, whereas only transiently (first 30 min of the 60 min test) reduced hedonic responses, without changes in aversive responses to intra-oral NaCl. Losartan intracerebroventricularly also only transiently (first 30 min) reduced the number of hedonic responses to intra-oral NaCl in euhydrated SHRs. The results suggest that NaCl palatability is increased and independent from body fluid balance in SHRs. The results also suggest that central AT1 receptors are part of the mechanisms activated to increase NaCl intake and palatability in SHRs. A partial dissociation between NaCl intake and palatability in SHRs is also suggested.
Asunto(s)
Captopril , Sodio , Animales , Captopril/farmacología , Furosemida/farmacología , Losartán/farmacología , Masculino , Ratas , Ratas Endogámicas SHRRESUMEN
The renin-angiotensin system (RAS) controls hypertonic NaCl intake driven by sodium appetite. Here we investigated whether the antagonism of RAS interferes with hedonic and aversive orofacial motor responses, or palatability, to intraoral infusion of 0.3 M NaCl (hNaCl). Adult rats were depleted of sodium by combined sc injection of furosemide and 24 h removal of ambient sodium. In experiment 1, losartan (AT1 angiotensin II receptor antagonist, intracerebroventricular, 200 µg/µl), produced a three-fold increase in aversive orofacial motor responses to hNaCl. Losartan also suppressed hNaCl intake recorded immediately thereafter. In experiment 2, each animal had repeated recordings of hNaCl intake and orofacial responses to hNaCl distributed for 180 min. Paired recordings of intake and orofacial responses occurred within five successive blocks after the recordings of only orofacial responses when the animals were still sodium deplete (block zero). Captopril (angiotensin converting enzyme blocker, intraperitoneal, 30 mg/kg) inhibited by 75% the hedonic orofacial responses to hNaCl in blocks zero and 1. The hedonic responses to captopril remained the same throughout blocks, but became similar to vehicle from blocks 2 to 5. There was no difference in aversive responses to 0.3 M NaCl between captopril and vehicle. Captopril produced a 70-100% inhibition of hNaCl intake in blocks 1 to 5. The results suggest that angiotensin II acts in the brain increasing the palatability of hypertonic sodium during the consummatory phase of sodium appetite.
Asunto(s)
Sistema Renina-Angiotensina , Sodio , Animales , Apetito , Captopril/farmacología , Losartán/farmacología , Ratas , Cloruro de SodioRESUMEN
Spontaneously hypertensive rats (SHRs) have increased daily or induced sodium intake compared to normotensive rats. In normotensive rats, angiotensin II (ANG II)-induced sodium intake is blocked by the inactivation of p42/44 mitogen-activated protein kinase, also known as extracellular signal-regulated protein kinase1/2 (ERK1/2). Here we investigated if inhibition of ERK1/2 pathway centrally would change sodium appetite and intracerebroventricular (icv) ANG II-induced pressor response in SHRs. SHRs (280-330 g, n = 07-14/group) with stainless steel cannulas implanted in the lateral ventricle (LV) were used. Water and 0.3 M NaCl intake was induced by the treatment with the diuretic furosemide + captopril (angiotensin converting enzyme blocker) subcutaneously or 24 h of water deprivation (WD) followed by 2 h of partial rehydration with only water (PR). The blockade of ERK1/2 activation with icv injections of U0126 (MEK1/2 inhibitor, 2 mM; 2 µl) reduced 0.3 M NaCl intake induced by furosemide + captopril (5.0 ± 1.0, vs. vehicle: 7.3 ± 0.7 mL/120 min) or WD-PR (4.6 ± 1.3, vs. vehicle: 10.3 ± 1.4 mL/120 min). PEP7 (selective inhibitor of AT1 receptor-mediated ERK1/2 activation, 2 nmol/2 µL) icv also reduced WD-PR-induced 0.3 M NaCl (2.8 ± 0.7, vs. vehicle: 6.8 ± 1.4 mL/120 min). WD-PR-induced water intake was also reduced by U0126 or PEP7. In addition, U0126 or PEP7 icv reduced the pressor response to icv ANG II. Therefore, the present results suggest that central AT1 receptor-mediated ERK1/2 activation is part of the mechanisms involved in sodium appetite and ANG II-induced pressor response in SHRs.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Angiotensina II/genética , Apetito/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Receptor de Angiotensina Tipo 1/genética , Animales , Apetito/genética , Butadienos/farmacología , Captopril/farmacología , Modelos Animales de Enfermedad , Furosemida/farmacología , Humanos , Hipertensión/genética , Hipertensión/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/genética , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Nitrilos/farmacología , Ratas , Ratas Endogámicas SHR , Sodio/metabolismoRESUMEN
Behavioral sensitization occurs during sodium appetite (expressed as sodium intake to compensate for depleted sodium) and need-free sodium intake (expressed as daily overnight sodium intake in excess of dietary sodium need). Previously, we found that a slow-onset sodium appetite protocol cross-sensitized need-free sucrose intake in sucrose-naïve adult rats. That is, a history of sodium depletion elevated later sucrose intake. The objective of the present work was, first, to investigate whether a protocol that evokes a rapid-onset (within 2 h) sodium appetite using furosemide along with a low dose captopril (Furo/Cap), also cross-sensitizes sucrose intake. Then, we investigated whether 1) sensitization of need-free 0.3 M NaCl intake interacts with need-free sucrose intake, and 2) MK-801, a glutamate NMDA receptor antagonist, inhibits cross-sensitization of sucrose intake. Groups received 3-4 Furo/Cap or vehicle treatments with 48/72-h intervals. We investigated sucrose intake in hydrated and fed conditions for 2 h/day for 5 days, starting 6-10 days after the last Furo/Cap treatment. Episodes of Furo/Cap sensitized need-free sodium intake, as expected. Similar to our prior work, the rapid-onset Furo/Cap protocol cross-sensitized sucrose intake in sucrose-naïve rats and had no persistent effect on blood biochemistry. MK-801 treatment along with Furo/Cap injections appeared to prevent cross-sensitization of sucrose consumption. Sucrose intake tests unexpectedly reduced sensitized need-free sodium intake. However, MK-801 treatment allowed a rebound in need-free sodium intake subsequent to the last sucrose intake test. The results suggest that plasticity in glutamatergic mechanisms mediate inverse and reciprocal interactions between the production of sodium appetite and sucrose intake.
Asunto(s)
Apetito , Sodio en la Dieta , Animales , Diuréticos/farmacología , Ratas , Ratas Sprague-Dawley , Sodio , AzúcaresRESUMEN
Excessive salt intake has been associated with the development or worsening of chronic diseases such as hypertension and spontaneously hypertensive rats (SHR) have a typical increased sodium preference. Estrogens reduce sodium appetite, but we do not know whether such effect relates to alterations in sodium palatability. Here we evaluated the influence of ovarian hormones on orofacial motor responses, an index of palatability, to intra-oral infusion of 0.3â¯M NaCl (IONaCl). Adult female SHR and normotensive Holtzman rats (HTZ) were used. Sodium appetite was produced by water deprivation followed immediately by partial rehydration by drinking water to satiation (WD-PR protocol). Immediately at the end of WD-PR, animals received an IO-NaCl for videotape recording of orofacial motor responses. At the end of IO-NaCl, they had access to two bottles containing 0.3â¯M NaCl and water to ingest (sodium appetite test). Bilateral ovariectomy (OVX) enhanced 0.3â¯M NaCl intake during the sodium appetite test and increased the frequency of orofacial hedonic responses to IO-NaCl in both strains. It had no effect on aversive responses. Estradiol treatment in SHR-OVX decreased hedonic responses and increased aversive responses to IO-NaCl. It also reduced 0.3â¯M NaCl intake during the sodium appetite test, but had no effect on baseline mean arterial pressure and heart rate. The results suggest that ovarian hormones restrain WD-PR-induced sodium appetite by reducing the hedonic properties of sodium taste. The results also suggest that estrogens mediate such reduction, particularly in SHR.
Asunto(s)
Estradiol/farmacología , Cloruro de Sodio/administración & dosificación , Privación de Agua , Animales , Femenino , Ovariectomía , Distribución Aleatoria , Ratas Endogámicas SHR , Ratas Sprague-Dawley , Gusto/fisiologíaRESUMEN
Achatina fulica snails cause environmental problems and represent a public health hazard since it is a host in the life cycles of various parasites, among them, Angiostrongylus cantonensis and, less frequently, Ancylostoma caninum. We report the occurrence of Angistrongylus cantonensis, as well as the unexpected finding of Ancylostoma caninum, in a total of 936 specimens of Achatina fulica snails from different regions of São Paulo city, Brazil. Samples were divided into 492 pools which were screened for nematodes. If present, larvae were submitted to DNA extraction and PCR protocol targeting, the ITS-2 gene junction. From the 183 positive pools for larvae presence, 97 showed specific 650 bp band at electrophoresis and 21 presented bands nearly 300 bp. Two amplicons from each size were and sequenced. A BLAST/n of 650 bp sequences presented identity with Angistrongylus cantonensis, while the two of 300 bp, showed identity with Ancylostoma caninum, also supported by phylogenetic analysis. This is the second report of Ancylostoma caninum found in these snails in the world, therefore, this study allows a better understanding about these diseases and highlights the need of continue systematically mapping sites that can be infested with the mollusc.
Os caramujos Achatina fulica causam problemas ambientais e representam um perigo em Saúde Pública uma vez que são hospedeiros de vários parasitas, entre eles o Angiostrongylus cantonensis e menos frequentemente o Ancylostoma caninum. Nós relatamos a ocorrência de Angistrongylus cantonensis, bem como o achado de Ancylostoma caninum, a partir de 936 espécimens de caramujos Achatina fulica de diferentes regiões da cidade de São Paulo, Brasil. Amostras foram divididas em 492 pools os quais foram triados para nematóides. Se presentes, larvas foram submetidas a extração de DNA e um protocolo de PCR tendo como alvo a junção do gene ITS-2. De 183 pools contendo larvas, 97 apresentaram bandas específicas de 650 pb e na eletroforese 21 apresentaram bandas próximas aos 300 pb. Dois amplicons de cada tamanho foram sequenciados. A submissão ao BLAST/n das sequências de 650 pb apresentaram identidade das sequências com Angistrongylus cantonensis, enquanto que as duas de 300 pb apresentaram identidade com Ancylostoma caninum, também corroboradas por análises filogenéticas. Este é o segundo relato do encontro de Ancylostoma caninum nestes caramujos no mundo, sendo assim, este estudo permite um melhor entendimento destas doenças e denota a necessidade de contínuo monitoramento de regiões que estejam infestadas pelo molusco.
Asunto(s)
Animales , Ancylostoma/aislamiento & purificación , Angiostrongylus cantonensis/aislamiento & purificación , Caracoles/parasitología , Caracoles/patogenicidad , Especies Introducidas/estadística & datos numéricosRESUMEN
Achatina fulica snails cause environmental problems and represent a public health hazard since it is a host in the life cycles of various parasites, among them, Angiostrongylus cantonensis and, less frequently, Ancylostoma caninum. We report the occurrence of Angistrongylus cantonensis, as well as the unexpected finding of Ancylostoma caninum, in a total of 936 specimens of Achatina fulica snails from different regions of São Paulo city, Brazil. Samples were divided into 492 pools which were screened for nematodes. If present, larvae were submitted to DNA extraction and PCR protocol targeting, the ITS-2 gene junction. From the 183 positive pools for larvae presence, 97 showed specific 650 bp band at electrophoresis and 21 presented bands nearly 300 bp. Two amplicons from each size were and sequenced. A BLAST/n of 650 bp sequences presented identity with Angistrongylus cantonensis, while the two of 300 bp, showed identity with Ancylostoma caninum, also supported by phylogenetic analysis. This is the second report of Ancylostoma caninum found in these snails in the world, therefore, this study allows a better understanding about these diseases and highlights the need of continue systematically mapping sites that can be infested with the mollusc.
Achatina fulica snails cause environmental problems and represent a public health hazard since it is a host in the life cycles of various parasites, among them, Angiostrongylus cantonensis and, less frequently, Ancylostoma caninum. We report the occurrence of Angistrongylus cantonensis, as well as the unexpected finding of Ancylostoma caninum, in a total of 936 specimens of Achatina fulica snails from different regions of São Paulo city, Brazil. Samples were divided into 492 pools which were screened for nematodes. If present, larvae were submitted to DNA extraction and PCR protocol targeting, the ITS-2 gene junction. From the 183 positive pools for larvae presence, 97 showed specific 650 bp band at electrophoresis and 21 presented bands nearly 300 bp. Two amplicons from each size were and sequenced. A BLAST/n of 650 bp sequences presented identity with Angistrongylus cantonensis, while the two of 300 bp, showed identity with Ancylostoma caninum, also supported by phylogenetic analysis. This is the second report of Ancylostoma caninum found in these snails in the world, therefore, this study allows a better understanding about these diseases and highlights the need of continue systematically mapping sites that can be infested with the mollusc.
RESUMEN
Achatina fulica snails cause environmental problems and represent a public health hazard since it is a host in the life cycles of various parasites, among them, Angiostrongylus cantonensis and, less frequently, Ancylostoma caninum. We report the occurrence of Angistrongylus cantonensis, as well as the unexpected finding of Ancylostoma caninum, in a total of 936 specimens of Achatina fulica snails from different regions of São Paulo city, Brazil. Samples were divided into 492 pools which were screened for nematodes. If present, larvae were submitted to DNA extraction and PCR protocol targeting, the ITS-2 gene junction. From the 183 positive pools for larvae presence, 97 showed specific 650 bp band at electrophoresis and 21 presented bands nearly 300 bp. Two amplicons from each size were and sequenced. A BLAST/n of 650 bp sequences presented identity with Angistrongylus cantonensis, while the two of 300 bp, showed identity with Ancylostoma caninum, also supported by phylogenetic analysis. This is the second report of Ancylostoma caninum found in these snails in the world, therefore, this study allows a better understanding about these diseases and highlights the need of continue systematically mapping sites that can be infested with the mollusc.(AU)
Os caramujos Achatina fulica causam problemas ambientais e representam um perigo em Saúde Pública uma vez que são hospedeiros de vários parasitas, entre eles o Angiostrongylus cantonensis e menos frequentemente o Ancylostoma caninum. Nós relatamos a ocorrência de Angistrongylus cantonensis, bem como o achado de Ancylostoma caninum, a partir de 936 espécimens de caramujos Achatina fulica de diferentes regiões da cidade de São Paulo, Brasil. Amostras foram divididas em 492 pools os quais foram triados para nematóides. Se presentes, larvas foram submetidas a extração de DNA e um protocolo de PCR tendo como alvo a junção do gene ITS-2. De 183 pools contendo larvas, 97 apresentaram bandas específicas de 650 pb e na eletroforese 21 apresentaram bandas próximas aos 300 pb. Dois amplicons de cada tamanho foram sequenciados. A submissão ao BLAST/n das sequências de 650 pb apresentaram identidade das sequências com Angistrongylus cantonensis, enquanto que as duas de 300 pb apresentaram identidade com Ancylostoma caninum, também corroboradas por análises filogenéticas. Este é o segundo relato do encontro de Ancylostoma caninum nestes caramujos no mundo, sendo assim, este estudo permite um melhor entendimento destas doenças e denota a necessidade de contínuo monitoramento de regiões que estejam infestadas pelo molusco.(AU)
Asunto(s)
Animales , Caracoles/parasitología , Caracoles/patogenicidad , Angiostrongylus cantonensis/aislamiento & purificación , Ancylostoma/aislamiento & purificación , Especies Introducidas/estadística & datos numéricosRESUMEN
Although folic acid (FA) supplementation is known to influence numerous physiological functions, especially during pregnancy, little is known about its direct effects on the mothers' health. However, this vitamin is essential for the health of the mother and for the normal growth and development of the fetus. Thus, the aim of this study was (1) to evaluate the cognitive effects and biochemical markers produced by the AIN-93 diet (control), the AIN-93 diet supplemented with different doses of FA (5, 10, and 50 mg/kg), and a FA-deficient diet during pregnancy and lactation in female mother rats (dams) and (2) to evaluate the effect of maternal diets on inflammatory parameters in the adult offspring which were subjected to an animal model of schizophrenia (SZ) induced by ketamine (Ket). Our study demonstrated through the Y-maze test that rats subjected to the FA-deficient diet showed significant deficits in spatial memory, while animals supplemented with FA (5 and 10 mg/kg) showed no deficit in spatial memory. Our results also suggest that the rats subjected to the FA-deficient diet had increased levels of carbonylated proteins in the frontal cortex and hippocampus and also increased plasma levels of homocysteine (Hcy). Folate was able to prevent cognitive impairments in the rats supplemented with FA (5 and 10 mg/kg), data which may be attributed to the antioxidant effect of the vitamin. Moreover, FA prevented protein damage and elevations in Hcy levels in the rats subjected to different doses of this vitamin (5, 10, and 50 mg/kg). We verified a significant increase of the anti-inflammatory cytokine (interleukin-4 (IL-4)) and a reduction in the plasma levels of proinflammatory cytokines (interleukin-6 (IL-6)) and TNF-α) in the dams that were subjected to the diets supplemented with FA (5, 10, and 50 mg/kg), showing the possible anti-inflammatory effects of FA during pregnancy and lactation. In general, we also found that in the adult offspring that were subjected to an animal model of SZ, FA had a protective effect in relation to the levels of IL-4, IL-6, and TNF-α, which indicates that the action of FA persisted in the adult offspring, since FA showed a lasting effect on the inflammatory response, which was similar in both the dams and their offspring. In conclusion, the importance of supplementation with FA during pregnancy and lactation should be emphasized, not only for the benefit of the offspring but also for the health of the mother. All this is due to the considerable protective effect of this vitamin against oxidative damage, cognitive impairment, hyperhomocysteinemia, immune function, and also its ability in preventing common processes in post-pregnancy stages, as well as in reducing the risks of neurodevelopmental disorders and enhancing fetal immune development.
Asunto(s)
Suplementos Dietéticos , Deficiencia de Ácido Fólico/dietoterapia , Ácido Fólico/administración & dosificación , Efectos Tardíos de la Exposición Prenatal/dietoterapia , Esquizofrenia/dietoterapia , Complejo Vitamínico B/administración & dosificación , Animales , Modelos Animales de Enfermedad , Femenino , Deficiencia de Ácido Fólico/inducido químicamente , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Ketamina/toxicidad , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratas , Ratas Wistar , Esquizofrenia/inducido químicamente , Esquizofrenia/metabolismoRESUMEN
The administration of cholinergic agonists like pilocarpine intraperitoneally (i.p.) or carbachol intracerebroventricularly (i.c.v.) induces water, but non significant hypertonic NaCl intake. These treatments also produce pressor responses, which may inhibit sodium intake. Noradrenaline (NOR) acting on α2-adrenoceptors in the lateral parabrachial nucleus (LPBN) deactivates inhibitory mechanisms increasing fluid depletion-induced sodium intake. In the present study, we investigated: (1) water and 1.8% NaCl intake in rats treated with pilocarpine i.p. or carbachol i.c.v. combined with NOR into the LPBN; (2) if inhibitory signals from cardiovascular receptors are blocked by NOR in the LPBN. Male Holtzman rats with stainless steel guide-cannulas implanted in the lateral ventricle and bilaterally in the LPBN were used. Bilateral injections of NOR (80nmol/0.2µl) into the LPBN decreased water intake (0.8±0.3, vs. saline (SAL): 2.9±0.3ml/180min) induced by pilocarpine (1mg/kg of body weight) i.p., without changing 1.8% NaCl intake (0.8±2.4, vs. SAL: 0.5±0.3ml/180min). Prazosin (1mg/kg of body weight) i.p. blocked pressor responses and increased water and 1.8% NaCl intake (6.3±1.7 and 14.7±3.5ml/180min, respectively) in rats treated with pilocarpine combined with NOR into the LPBN. Prazosin i.p. also increased 1.8% NaCl intake in rats treated with carbachol i.c.v combined with NOR into the LPBN. The results suggest that different signals inhibit sodium intake in rats treated with cholinergic agonists, among them those produced by increases of arterial pressure that are not efficiently deactivated by NOR acting in the LPBN.
Asunto(s)
Agonistas Colinérgicos/farmacología , Ingestión de Líquidos/fisiología , Norepinefrina/metabolismo , Núcleos Parabraquiales/metabolismo , Cloruro de Sodio Dietético , Animales , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Carbacol/farmacología , Catéteres de Permanencia , Ingestión de Líquidos/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Masculino , Núcleos Parabraquiales/efectos de los fármacos , Pilocarpina/farmacología , Prazosina/farmacología , Ratas Sprague-DawleyRESUMEN
Central α2-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α2-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α2-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α2-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α2-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α2-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.
Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Líquidos Corporales/efectos de los fármacos , Homeostasis/efectos de los fármacos , Núcleos Parabraquiales/efectos de los fármacos , Agonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Animales , Líquidos Corporales/fisiología , Captopril/administración & dosificación , Captopril/farmacología , Ingestión de Líquidos/efectos de los fármacos , Furosemida/administración & dosificación , Furosemida/farmacología , Homeostasis/fisiología , Imidazoles/administración & dosificación , Imidazoles/farmacología , Núcleos Parabraquiales/fisiología , Ratas , Cloruro de Sodio DietéticoRESUMEN
Injections of noradrenaline into the lateral parabrachial nucleus (LPBN) increase arterial pressure and 1.8% NaCl intake and decrease water intake in rats treated with the diuretic furosemide (FURO) combined with a low dose of the angiotensin converting enzyme inhibitor captopril (CAP). In the present study, we investigated the influence of the pressor response elicited by noradrenaline injected into the LPBN on FURO+CAP-induced water and 1.8% NaCl intake. Male Holtzman rats with bilateral stainless steel guide-cannulas implanted into LPBN were used. Bilateral injections of noradrenaline (40 nmol/0.2 µl) into the LPBN increased FURO+CAP-induced 1.8% NaCl intake (12.2±3.5, vs., saline: 4.2±0.8 ml/180 min), reduced water intake and strongly increased arterial pressure (50±7, vs. saline: 1±1 mmHg). The blockade of the α1 adrenoceptors with the prazosin injected intraperitoneally abolished the pressor response and increased 1.8% NaCl and water intake in rats treated with FURO+CAP combined with noradrenaline injected into the LPBN. The deactivation of baro and perhaps volume receptors due to the cardiovascular effects of prazosin is a mechanism that may facilitate water and NaCl intake in rats treated with FURO+CAP combined with noradrenaline injected into the LPBN. Therefore, the activation of α2 adrenoceptors with noradrenaline injected into the LPBN, at least in dose tested, may not completely remove the inhibitory signals produced by the activation of the cardiovascular receptors, particularly the signals that result from the extra activation of these receptors with the increase of arterial pressure.
Asunto(s)
Norepinefrina/farmacología , Prazosina/farmacología , Sodio/administración & dosificación , Núcleo Solitario/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Sistema Cardiovascular/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Norepinefrina/metabolismo , Prazosina/administración & dosificación , Ratas , Ratas Sprague-Dawley , Núcleo Solitario/metabolismoRESUMEN
The deactivation of the inhibitory mechanisms with injections of moxonidine (α2-adrenoceptor/imidazoline receptor agonist) into the lateral parabrachial nucleus (LPBN) increases hypertonic NaCl intake by intra- or extracellular dehydrated rats. In the present study, we investigated the changes in the urinary sodium and volume, sodium balance, and plasma vasopressin and oxytocin in rats treated with intragastric (i.g.) 2 M NaCl load (2 ml/rat) combined with injections of moxonidine into the LPBN. Male Holtzman rats (n=5-12/group) with stainless steel cannulas implanted bilaterally into LPBN were used. Bilateral injections of moxonidine (0.5 nmol/0.2 µl) into the LPBN decreased i.g. 2 M NaCl-induced diuresis (4.6±0.7 vs. vehicle: 7.4±0.6 ml/120 min) and natriuresis (1.65±0.29 vs. vehicle: 2.53±0.17 mEq/120 min), whereas the previous injection of the α2-adrenoceptor antagonist RX 821002 (10 nmol/0.2 µl) into the LPBN abolished the effects of moxonidine. Moxonidine injected into the LPBN reduced i.g. 2 M NaCl-induced increase in plasma oxytocin and vasopressin (14.6±2.8 and 2.2±0.3 vs. vehicle: 25.7±7 and 4.3±0.7 pg/ml, respectively). Moxonidine injected into the LPBN combined with i.g. 2 M NaCl also increased 0.3 M NaCl intake (7.5±1.7 vs. vehicle: 0.5±0.2 mEq/2 h) and produced positive sodium balance (2.3±1.4 vs. vehicle: -1.2±0.4 mEq/2 h) in rats that had access to water and NaCl. The present results show that LPBN α2-adrenoceptor activation reduces renal and hormonal responses to intracellular dehydration and increases sodium and water intake, which facilitates sodium retention and body fluid volume expansion.
Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Plexo Braquial , Deshidratación/metabolismo , Hormonas/sangre , Imidazoles/farmacología , Receptores de Imidazolina/agonistas , Riñón/efectos de los fármacos , Agonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Antagonistas Adrenérgicos alfa/farmacología , Animales , Arginina Vasopresina/sangre , Factor Natriurético Atrial/sangre , Volumen Sanguíneo/efectos de los fármacos , Deshidratación/patología , Diuresis/efectos de los fármacos , Idazoxan/análogos & derivados , Idazoxan/farmacología , Imidazoles/administración & dosificación , Receptores de Imidazolina/administración & dosificación , Riñón/citología , Masculino , Natriuresis/efectos de los fármacos , Concentración Osmolar , Oxitocina/sangre , Potasio/orina , Ratas , Ratas Sprague-Dawley , Renina/sangre , Sodio/sangre , Sodio/metabolismo , Cloruro de Sodio/farmacología , Equilibrio Hidroelectrolítico/efectos de los fármacosRESUMEN
Introducción: Los catéteres venosos centrales (CVC) plantean un alto riesgo de infección. La infección del sitio de salida (ISS-CVC) es la menos estudiada, y se desconoce su asociación con la bacteriemia asociada a catéter (BAC) y su impacto en la evolución del paciente. Objetivo: Evaluar la asociación entre ISS-CVC, BAC y mortalidad. Materiales y métodos: Estudio prospectivo, de observación. Pacientes internados en una Unidad de Terapia Intensiva médico/quirúrgica que requirieron la colocación de CVC desde el 01/06/2010 hasta el 01/04/2012. Se evaluaron datos epidemiológicos, BAC (según criterios de los CDC) y gérmenes. Se utilizaron media ± DE, mediana y rango intercuartílico, y porcentajes. Resultados: Durante este período, ingresaron 575 pacientes, el 98% requirió CVC. Datos de los pacientes: edad 41 ± 26 años, APACHE II 15 ± 7, 96% con ventilación mecánica, días de ventilación mecánica 41 (33-63), días de internación 43 (25-67). Todos los CVC con ISS fueron retirados y cultivados. Se observaron 51 ISS: 5,5/1000-días-catéter: 33% subclavia, 38% yugular, 29% femoral. Seis pacientes con ISS (12%) tuvieron BAC (0,65/1000-días-catéter): 3 subclavias, 2 yugulares, 1 femoral; 2 con halo y 8 con secreción purulenta. Tiempo de permanencia del CVC: 7,5 días (5-10). Clínica al momento de la ISS: shock 50%, fiebre 83%, SOFA 6 ± 3. El 83% de las infecciones fueron monomicrobianas: 83% por bacilos gramnegativos (2 Klebsiella, 2 Pseudomonas, 1 Serratia y 1 Acinetobacter), 17% por enterococos resistentes a vancomicina. La mortalidad fue del 50%. Conclusión: Aunque la ISS provocó una baja incidencia de BAC, la mortalidad fue alta. Al parecer, la ISS no es un factor predictivo de BAC.(AU)
Introduction: Central venous catheters (CVC) are widely used and pose a high risk of infection. There are few studies on insertion site infection (ISI-CVC), and both its association with catheter-associated bloodstream infection (CABSI) and the outcome of patients are unknown. Objective: To determine the association between ISI-CVC, the presence of CABSI and mortality. Materials and methods: Prospective observational study. All patients admitted to a medical/surgical Intensive Care Unit requiring CVC insertion from 06/01/2010 to 04/01/2012 were included. Epidemiological data, CABSI (according to CDC criteria) and microorganisms involved were evaluated. Mean ± SD, median and interquartile range, and percentages were used. Results: During the period study, 575 patients were admitted, 98% required CVC. Patient´s data: age 41 ± 26 years, APACHE II 15 ± 7, 96% on mechanical ventilation, days on mechanical ventilation: 41 (33-63), length of stay 43 (25-67) days. All CVCs with ISI were removed and cultured. Fifty one ISI were observed (5.5/1000-catheter-day). Six patients with ISI (12%) presented CABSI (0.65/1000-catheter-day): 3 in subclavian, 2 in jugular, 1 femoral; 2 with erythema and 8 with purulent secretion. CVC permanence: 7.5 day (5-10). Signs and/or symptoms at the moment of ISI: shock 50%, fever 83%, SOFA 6 ± 3. The 83% of infections were caused by one microorganism: 83% due to gram-negative bacilli (2 Klebsiella, 2 Pseudomonas, 1 Serratia, and 1 Acinetobacter), 17% due to vancomycin-resistant enterococci. The mortality rate was 50%. Conclusion: Although ISI-CVC presented a low incidence of CABSI, mortality rate was high. The ISI-CVC might have a little predictable value for CABSI.(AU)
Asunto(s)
Humanos , Bacteriemia/mortalidad , Catéteres Venosos Centrales , Infecciones , MortalidadRESUMEN
The blockade of the inhibitory mechanisms for sodium intake with GABAergic activation in the lateral parabrachial nucleus (LPBN) induces strong ingestion of water and hypertonic NaCl in satiated and normovolemic rats. A question that remains is if the activity of facilitatory mechanisms, like angiotensin II, is necessary for sodium and water intake induced by muscimol (GABA(A) receptor agonist) injected into the LPBN. Therefore, in the present study, we investigated the effects of the blockade of angiotensinergic AT(1) receptors with losartan injected i.c.v. on 0.3 M NaCl and water intake induced by muscimol injected into the LPBN in satiated and normovolemic rats. Male Holtzman rats with stainless steel cannulas implanted bilaterally into the LPBN and unilaterally into the lateral ventricle were used. Bilateral injections of muscimol (0.5 nmol/0.2 µl) into the LPBN combined with i.c.v. injection of vehicle induced 0.3 M NaCl (31.7 ± 1.8 ml/240 min, vs. saline: 0.4 ± 0.3 ml/240 min) and water intake (21.5 ± 1.9 ml/240 min, vs. saline: 0.8 ± 0.2 ml/240 min). Losartan (50 and 100 µg/1.0 µl) injected i.c.v. reduced the effects of LPBN-muscimol on 0.3 M NaCl (18.9 ± 1.9 and 9.9 ± 1.7 ml/240 min, respectively) and water intake (9.8 ± 1.7 and 5.1 ± 1.1 ml/240 min, respectively). The results suggest that the activation of central AT(1) angiotensinergic receptors is essential for hypertonic NaCl and water intake induced by the blockade of the inhibitory mechanisms with muscimol injected into the LPBN in satiated and normovolemic rats.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Ingestión de Líquidos/fisiología , Agonistas de Receptores de GABA-A/farmacología , Losartán/farmacología , Muscimol/farmacología , Puente/fisiología , Angiotensina II/fisiología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Animales , Ingestión de Líquidos/efectos de los fármacos , Agonistas de Receptores de GABA-A/administración & dosificación , Inyecciones Intraventriculares , Losartán/administración & dosificación , Masculino , Microinyecciones , Muscimol/administración & dosificación , Muscimol/antagonistas & inhibidores , Puente/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Solución Salina HipertónicaRESUMEN
Lipopolysaccharide (LPS), an endotoxin from the wall of Escherichia coli, produces a general behavioral inhibition and affects several aspects of fluid-electrolyte balance. LPS inhibits thirst; however, it is not clear if it also inhibits sodium appetite. The present results show that LPS (0.3-2.5 mg/kg body wt) injected intraperitoneally produces a dose-dependent reduction of sodium appetite expressed as 0.3 M NaCl intake induced by sodium depletion (furosemide plus removal of ambient sodium for 24 h). The high doses of LPS (1.2-2.5 mg/kg) also produced transient hypothermia at the beginning of the sodium appetite test; however, no dose produced hyperthermia. LPS also increased the stomach liquid content (an index of gastric emptying) after a load of 0.3 M NaCl given intragastrically by gavage to sodium-depleted rats. The α(2)-adrenoceptor antagonist yohimbine (5 mg/kg ip) abolished the effect of LPS on 0.3 M NaCl intake, without changing the effect of LPS on gastric emptying. Injection of RX-821002 (160 nmol), another α(2)-adrenoceptor antagonist, in the lateral cerebral ventricle (LV) also reversed the inhibition of sodium appetite produced by LPS. Yohimbine intraperitoneally or RX-821002 in the LV alone had no effect on sodium intake. Although yohimbine plus LPS produced a slight hypotension, RX-821002 plus LPS produced no change in arterial pressure, suggesting that the blockade of the effects of LPS on sodium intake by the α(2)-adrenoceptor antagonists is independent from changes in arterial pressure. The results suggest an inhibitory role for LPS in sodium appetite that is mediated by central α(2)-adrenoceptors.
Asunto(s)
Apetito/efectos de los fármacos , Lipopolisacáridos/farmacología , Receptores Adrenérgicos alfa 2/fisiología , Cloruro de Sodio Dietético/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Animales , Apetito/fisiología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Temperatura Corporal/efectos de los fármacos , Temperatura Corporal/fisiología , Relación Dosis-Respuesta a Droga , Vaciamiento Gástrico/efectos de los fármacos , Vaciamiento Gástrico/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Idazoxan/análogos & derivados , Idazoxan/farmacología , Inyecciones Intraperitoneales , Lipopolisacáridos/administración & dosificación , Masculino , Modelos Animales , Ratas , Ratas Sprague-Dawley , Receptores Adrenérgicos alfa 2/efectos de los fármacos , Yohimbina/farmacologíaRESUMEN
GABA(A) and GABA(B) receptors are present in the lateral parabrachial nucleus (LPBN), a pontine area involved with inhibitory mechanisms related to the control of sodium appetite. Activation of GABA(A) receptors in the LPBN induces strong ingestion of 0.3 M sodium chloride (NaCl) in normonatremic and euhydrated rats. In the present study, we investigated the effects of the GABA(B) receptor agonist baclofen, injected alone or combined with GABA(A) or GABA(B) receptor antagonists into the LPBN on 0.3 M NaCl, water, 0.06 M sucrose and food intake in normonatremic and euhydrated rats. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN were used. In normonatremic and euhydrated rats, bilateral injections of baclofen (0.5 nmol/0.2 µl) into the LPBN induced 0.3 M NaCl (24.0±3.1 vs. saline: 2.0±0.8 ml/240 min) and water intake (10.6±1.4 vs. saline: 3.5±0.7 ml/240 min) in a two-bottle test. Injections of GABA(B) receptor antagonists CGP 35348 (50 nmol/0.2 µl) or 2-hydroxysaclofen (5 nmol/0.2 µl) or GABA(A) receptor antagonist bicuculline (1.6 nmol/0.2 µl) into the LPBN reduced 0.3 M NaCl (14.1±4.7 ml/240 min; 9.97±2.5 ml/210 min; 8.8±5.9 ml/240 min, respectively) and water intake induced by baclofen injected into the LPBN. Baclofen (0.5 nmol/0.2 µl) injected into the LPBN also induced 0.06 M sucrose intake (21.8±5.9 vs. saline: 5.0±2.6 ml/180 min). Urinary volume and sodium excretion had a tendency to decrease after baclofen injection into the LPBN, whereas arterial pressure and food intake were not affected. The results show that baclofen injected into the LPBN, in normonatremic and euhydrated rats, produces a natriorexigenic effect dependent on GABA(A) and GABA(B) receptor activation. The natriorexigenic effect is not secondary to alterations in blood pressure or sodium urinary excretion. In addition, baclofen injected into the LPBN also induces 0.06 M sucrose intake.