RESUMO
Introducción: Se ha postulado que el uso de vasopresina tendría efectos beneficiosos en el postoperatorio de cirugía cardiovascular. Objetivo: Evaluar la respuesta a la vasopresina en el postoperatorio (POP) de cirugía de Fontan de nuestra población. Métodos: Estudio de casos y controles anidados en una cohorte retrospectiva. Se incluyeron pacientes con cirugía de Fontan entre 2014 y 2019. Se registraron variables demográficas, datos del cateterismo pre-Fontan, días de asistencia respiratoria mecánica (ARM), necesidad de inotrópicos, diuréticos, diálisis, dieta hipograsa, octreotide, sildenafil y nutrición parenteral total (NPT); balance de fluidos al primer y segundo día POP, necesidad de cateterismo en el POP, días de permanencia de tubo pleural, días de internación, necesidad de reinternación y mortalidad. Se compararon los grupos con y sin vasopresina utilizando la prueba de Mann- Whitney-Wilcoxon test. Se consideró significativa una p < 0.05. Resultados: Del total analizado, 35 pacientes recibieron vasopresina. En el grupo control fueron 58 pacientes con características similares de gravedad sin vasopresina. No se encontraron diferencias en la evolución postoperatoria entre ambos grupos. El grupo con vasopresina recibió en mayor proporción dieta hipograsa. Conclusiones: En nuestra serie el uso de vasopresina no marcó diferencias significativas en términos de morbimortalidad con relación al grupo control (AU)
Introduction: The use of vasopressin has been suggested to have beneficial effects in the postoperative period after cardiovascular surgery. Objective: To evaluate the response to vasopressin in the postoperative period (POP) of Fontan surgery in our population. Methods: Nested case-control study in a retrospective cohort. Patients who underwent Fontan surgery between 2014 and 2019 were included. Demographic variables, pre-Fontan catheterization data, days of mechanical ventilation (MRA), need for inotropics, diuretics, dialysis, low-fat diet, octreotide, sildenafil and total parenteral nutrition (TPN); fluid balance at first and second day POP, need for catheterization at POP, duration of chest tube drainage, days of hospitalization, need for readmission, and mortality were recorded. Groups with and without vasopressin were compared using the Mann-Whitney- Wilcoxon test. A p < 0.05 was considered significant. Results: Of all patients analyzed, 35 received vasopressin. The control group consisted of 58 patients with similar severity characteristics who did not receive vasopressin. No differences were found in the postoperative outcome between the two groups. The vasopressin group received a higher proportion of low-fat diet. Conclusions: In our series the use of vasopressin did not show significant differences in terms of morbidity and mortality compared to the control group (AU)
Assuntos
Humanos , Lactente , Pré-Escolar , Complicações Pós-Operatórias/tratamento farmacológico , Arginina Vasopressina/administração & dosagem , Arginina Vasopressina/uso terapêutico , Técnica de Fontan/efeitos adversos , Antidiuréticos/administração & dosagem , Antidiuréticos/uso terapêutico , Indicadores de Morbimortalidade , Estudos Retrospectivos , Resultado do Tratamento , HemodinâmicaRESUMO
RATIONALE: The amygdala plays a paramount role in the modulation of anxiety and numerous studies have shown that arginine vasopressin (AVP) elicits anxiogenic effects following either its systemic or septal administration. OBJECTIVES: The aim of this paper was to study the involvement of vasopressinergic neurotransmission in the amygdaloid modulation of unconditioned anxiety and to ascertain whether or not AVP receptor subtypes may have a differential role in this modulation. METHODS: Anxiety behavior was evaluated both in Shock-Probe Burying Test and Light-Dark Box following the bilateral microinfusion of AVP alone or AVP together with either AVP 1a or AVP 1b receptor antagonists into the central amygdala (CeA). RESULTS: AVP microinfusion elicited at low (1 ng/side) but not at high doses (10 ng/side) anxiogenic-like responses in the Shock-Probe Burying Test but not in the Light-Dark Box. SSR149415, an AVP 1b antagonist unlike Manning compound, an AVP 1a antagonist, fully prevented AVP effects in the Shock-Probe Burying Test when it was administered simultaneously with AVP. In addition, oxytocin receptor blockade also failed to affect AVP effects. No effects of any AVP antagonist by itself were observed in both anxiety paradigms. CONCLUSIONS: Our results indicate that AVP 1b receptor contribute to the amygdaloid modulation of anxiety at least in the context of the Shock-Probe Burying Test since no effects were noticed in the Light-Dark Box. It remains to the future to ascertain whether AVP receptor subtypes have indeed differential actions either in the modulation of global or specific features of unconditioned anxiety.
Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Ansiedade/metabolismo , Arginina Vasopressina/administração & dosagem , Receptores de Vasopressinas/metabolismo , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos/administração & dosagem , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Antagonistas de Hormônios/administração & dosagem , Masculino , Microinjeções , Ratos , Ratos Wistar , Receptores de Vasopressinas/agonistasRESUMO
A high-salt diet can lead to hydromineral imbalance and increases in plasma sodium and osmolality. It is recognized as one of the major contributing factors for cardiovascular diseases such as hypertension. The paraventricular nucleus (PVN) plays a pivotal role in osmotically driven sympathoexcitation and high blood pressure, the precise mechanisms of which are not fully understood. Recent evidence indicates that AVP released from magnocellular neurons might be involved in this process. Using a combination of in vivo and in situ studies, we sought to investigate whether AVP, acting on PVN neurons, can change mean arterial pressure (MAP) and sympathetic nerve activity (SNA) in euhydrated male rats. Furthermore, we wanted to determine whether V1a receptors on PVN neurons would be involved in salt-induced sympathoexcitation and hypertension. In rats, 4 days of salt loading (NaCl 2%) elicited a significant increase in plasma osmolality (39 ± 7 mosmol/kgH2O), an increase in MAP (26 ± 2 mmHg, P < 0.001), and sympathoexcitation compared with euhydrated rats. Microinjection of AVP into the PVN of conscious euhydrated animals (100 nl, 3 µM) elicited a pressor response (14 ± 2 mmHg) and a significant increase in lumbar SNA (100 nl, 1 mM) (19 ± 5%). Pretreatment with a V1a receptor antagonist, microinjected bilaterally into the PVN of salt-loaded animals, elicited a decrease in lumbar SNA (-14 ± 5%) and MAP (-19 ± 5 mmHg), when compared with the euhydrated group. Our findings show that AVP plays an important role in modulating the salt-induced sympathoexcitation and high blood pressure, via V1a receptors, within the PVN of male rats. As such, V1a receptors in the PVN might contribute to neurogenic hypertension in individuals consuming a high-salt diet.
Assuntos
Arginina Vasopressina/metabolismo , Pressão Arterial , Hipertensão/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Receptores de Vasopressinas/metabolismo , Cloreto de Sódio na Dieta , Sistema Nervoso Simpático/metabolismo , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos/administração & dosagem , Arginina Vasopressina/administração & dosagem , Pressão Arterial/efeitos dos fármacos , Modelos Animais de Doenças , Hipertensão/etiologia , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Masculino , Microinjeções , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Ratos Wistar , Receptores de Vasopressinas/agonistas , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiopatologia , Fatores de TempoRESUMO
The periaqueductal gray area (PAG) is a mesencephalic area involved in cardiovascular modulation. Noradrenaline (NA), a neurotransmitter involved in central blood pressure control, is present in the rat PAG. We report here on the cardiovascular effects caused by NA microinjection into the ventrolateral PAG (vlPAG) of unanesthetized rats and the peripheral mechanism involved in their mediation. NA microinjection in the vlPAG of unanesthetized rats evoked dose-related pressor and bradycardiac responses. No significant cardiovascular responses were observed in urethane-anesthetized rats. The pressor response was potentiated by pretreatment with the ganglion blocker pentolinium (5 or 10 mg/kg, intravenously). Pretreatment with the vasopressin antagonist dTyr(CH2)5 (Me)AVP (50 microg/kg, intravenously) blocked the pressor response evoked by the NA microinjection into the vlPAG. Additionally, circulating vasopressin content was found to be significantly increased after NA microinjection in the vlPAG. The results suggest that activation of noradrenergic synapses within the vlPAG modulates vasopressin release in unanesthetized rats.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Norepinefrina/administração & dosagem , Substância Cinzenta Periaquedutal , Vasoconstritores/administração & dosagem , Anestésicos Intravenosos , Animais , Arginina Vasopressina/administração & dosagem , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Esquema de Medicação , Sinergismo Farmacológico , Bloqueadores Ganglionares/administração & dosagem , Bloqueadores Ganglionares/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Antagonistas de Hormônios/administração & dosagem , Antagonistas de Hormônios/farmacologia , Injeções Intravenosas , Masculino , Microinjeções , Norepinefrina/antagonistas & inibidores , Norepinefrina/farmacologia , Tartarato de Pentolínio/administração & dosagem , Tartarato de Pentolínio/farmacologia , Ratos , Ratos Wistar , Uretana , Vasoconstritores/antagonistas & inibidores , Vasoconstritores/farmacologia , Vasopressinas/antagonistas & inibidores , Vasopressinas/sangueRESUMO
BACKGROUND: In addition to their role of sensing O2, pH, CO2, osmolarity and temperature, carotid body receptors (CBR) were proposed by us and others to have a glucose-sensing role in the blood entering the brain, integrating information about blood glucose and O2 levels essential for central nervous system (CNS) metabolism. The nucleus tractus solitarius (NTS) is an important relay station in central metabolic control and receives signals from peripheral glucose-sensitive hepatoportal afferences, from central glucose-responsive neurons in the brainstem and from CBR and arginine-vasopressin (AVP)-containing axons from hypothalamic nuclei. METHODS: In normal Wistar rats anesthetized with pentobarbital, permanent cannulas were placed stereotaxically in the NTS. Glucose changes were induced in vivo after CBR stimulation with sodium cyanide (NaCN-5 microg/100 g), preceded by an infusion of AVP [(10 or 40 pmol/100 nL of artificial cerebrospinal fluid) aCSF] or an antagonist for V1a receptors (anti-glycogenolytic vasopressin analogue-VP1-A) (100 pmol/100 nL of aCSF) into the NTS. RESULTS: CBR stimulation after an AVP infusion (larger dose) into the NTS resulted in a significantly higher arterial glucose and lower brain arterial-venous glucose difference. In the same way, VP1-A administration in the NTS significantly decreased the effects observed after AVP priming before CBR stimulation or preceding the CBR stimulation, alone. CONCLUSIONS: We propose that AVP in the NTS could participate in glucose homeostasis, modulating the information arising in CBR after histotoxic-anoxia stimulation.
Assuntos
Arginina Vasopressina/farmacologia , Corpo Carotídeo/efeitos dos fármacos , Células Quimiorreceptoras/metabolismo , Núcleo Solitário/efeitos dos fármacos , Animais , Arginina Vasopressina/administração & dosagem , Glicemia/metabolismo , Corpo Carotídeo/citologia , Corpo Carotídeo/metabolismo , Células Quimiorreceptoras/citologia , Homeostase , Masculino , Microinjeções , Ratos , Ratos Wistar , Reflexo , Cianeto de Sódio/administração & dosagem , Cianeto de Sódio/metabolismo , Núcleo Solitário/anatomia & histologia , Núcleo Solitário/metabolismoRESUMO
It has been reported that systemic injection of arginine vasopressin (AVP) induces a drop in body core temperature (T(c)), but little is known about the mechanisms involved. Because glutamate is an important excitatory neurotransmitter involved in a number of thermoregulatory actions, in the present study, we tested the hypothesis that glutamate plays a role in systemic AVP-induced hypothermia. Wistar rats were pretreated intracerebroventricularly (icv) with kynurenic acid, an antagonist of l-glutamate ionotropic receptors, alpha-methyl-(4-carboxyphenyl)glycine (MCPG), an antagonist of l-glutamate metabotropic receptors, or saline 15 min before intravenous injection of AVP (2 microg/kg) or saline. T(c), brown adipose tissue (BAT) temperature, blood pressure, heart rate, and tail skin temperature were measured continuously. Administration of saline icv followed by intravenous AVP caused a significant drop in T(c) brought about by a reduction in BAT thermogenesis and an increase in heat loss through the tail. MCPG treatment (icv) did not affect the fall in T(c) induced by AVP. Treatment with kynurenic acid (icv) abolished AVP-induced hypothermia but did not affect the AVP-evoked rise in blood pressure or drop in heart rate and BAT temperature. Heat loss through the tail was significantly reduced in animals injected with AVP and pretrated with kynurenic acid. These data indicate that ionotropic receptors of l-glutamate in the central nervous system participate in peripheral AVP-induced hypothermia by affecting heat loss through the tail.
Assuntos
Arginina Vasopressina , Ácido Glutâmico/metabolismo , Glicina/administração & dosagem , Hipotermia/induzido quimicamente , Hipotermia/fisiopatologia , Tecido Adiposo Marrom/fisiopatologia , Animais , Arginina Vasopressina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Regulação da Temperatura Corporal/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Glicina/análogos & derivados , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas , Injeções Intraventriculares , Ácido Cinurênico/administração & dosagem , Masculino , Ratos , Ratos Wistar , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Cauda/fisiopatologia , Termogênese/efeitos dos fármacosRESUMO
To evaluate the role of vasopressin (AVP) on blood pressure (BP) in diabetic patients with autonomic neuropathy (AN), 10 patients were studied on a fixed sodium and potassium diet. On days 4 and 7, a 24-h BP monitoring, as well as blood and urine samples for sodium, potassium, creatinine, and osmolality determinations were obtained for every 4-h period; either placebo or an AVP-V1-antagonist (d(CH2)5Tyr(me)AVP; 0.5 mg; AVPi) were given iv at 1 PM. On placebo, systolic BP (SBP) showed a progressive elevation during the day, declining after 12 PM (8 AM to 12 AM 122+/-9; 12 AM to 4 PM 125+/-11; 4 PM to 8 PM 134+/-14; 8 PM to 12 PM 136+/-14; 12 PM to 8 AM 131+/-17 mm Hg). On AVPi this rise in SBP was blunted: 8 AM to 12 AM 125+/-122; 12 AM to 4 PM 121+/-21; 4 PM to 8 PM 126+/-16; 8 PM to 12 PM 129+/-14; 12 PM to 8 AM 124+/-12 mm Hg. Creatinine clearance and diureses were greater during the night, both with placebo and AVPi. Plasma osmolality did not change on either day, although serum sodium decreased after AVPi, reaching the lowest values at 4 PM to 8 PM period (137+/-4.7 v 131+/-3.8 mEq/L; P < .05). With placebo, fractional excretion of sodium (FENa) increased from 0.43%+/-0.32% during 12 h of orthostasis to 0.92%+/-1.05% during 12 h of recumbency (P < .02). With AVPi, the FENa on orthostasis did not differ from that with placebo, although BP values were lower and did not increase with recumbency (0.58+/-0.57 v 0.73%+/-0.49%; NS). In conclusion, our results show that in diabetic patients with AN, vasopressin participates in BP control by stimulating vascular and renal V1 receptors, which results in vasoconstriction and sodium reabsorption.
Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Neuropatias Diabéticas/fisiopatologia , Vasopressinas/fisiologia , Adulto , Aldosterona/sangue , Arginina Vasopressina/administração & dosagem , Arginina Vasopressina/análogos & derivados , Pressão Sanguínea/efeitos dos fármacos , Feminino , Antagonistas de Hormônios/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Renina/sangue , Sódio/sangue , Sódio/urina , Vasopressinas/antagonistas & inibidores , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
The alpha2-adrenergic agonist clonidine and the neuropeptide oxytocin, inhibit sodium intake when injected intracerebroventricularly (i.c.v.). The present work investigates whether (1) vasopressin also inhibits sodium intake when injected i.c.v., and (2) the effect of oxytocin and of vasopressin on sodium intake is affected by i.c.v. injection of idazoxan, an alpha2-adrenergic antagonist. Clonidine (30 nmol), oxytocin (40, 80 nmol) and vasopressin (40, 80 nmol) were injected i.c.v. 20 min prior to a 1.5% NaCl appetite test, in rats depleted of sodium for 24 h by a combination of a single s.c. injection of furosemide (10 mg/rat) and removal of ambient sodium. Every dose of clonidine, oxytocin and vasopressin inhibited the 1.5% NaCl intake. Seizures were observed with the higher dose of vasopressin, but not with either dose of oxytocin. The effect of i.c.v. injection of clonidine (30 nmol), oxytocin (80 nmol) or vasopressin (40 nmol) was partially inhibited by prior i.c.v. injection of idazoxan (160, 320 nmol). The results suggest that the inhibition of 1.5% NaCl intake induced by i.c.v. injection of neuropeptides in sodium-depleted rats depends, in part, on the activation of central alpha2-adrenoceptors.
Assuntos
Antagonistas Adrenérgicos alfa/administração & dosagem , Arginina Vasopressina/administração & dosagem , Idazoxano/administração & dosagem , Ocitocina/administração & dosagem , Sódio na Dieta/administração & dosagem , Sódio/deficiência , Agonistas alfa-Adrenérgicos/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Clonidina/administração & dosagem , Injeções Intraventriculares , Masculino , Ratos , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Receptores Adrenérgicos alfa 2/fisiologiaRESUMO
We sought to determine whether arginine vasopressin (AVP) modulates arterial pressure (AP) by a receptor-mediated action in the nucleus reticularis rostroventrolateralis (nRVL). Immunocytochemical labeling with an antiserum against a synthetic AVP conjugate revealed a discrete although modest presumptive neuropeptidergic innervation of the nRVL. Electron microscopic analysis of vasopressinergic processes in the nRVL revealed that AVP-like immunoreactivity (AVP-LI) was primarily in axons and axon terminals. Immunoreactive terminals contained numerous small clear vesicles and large dense core vesicles and formed synapses with unlabeled dendrites. In the nRVL, retrograde transport-immunofluorescence data demonstrated close appositions between vasopressinergic beaded processes and a compact subambigual column of reticulospinal neurons labeled by deposits of cholera toxin beta-subunit into the thoracic spinal cord. Similar methods were used to define the origins of the AVP-afferent projection to nRVL. These retrograde transport-immunofluorescence studies demonstrated numerous retrogradely labeled neurons in the hypothalamus, including the paraventricular nucleus (PVN), after injections of a retrograde tracer, Fluoro-Gold into the ventrolateral medulla. However, double-labeled neurons were rare and confirmed a diffuse AVP afferent innervation of the sympathoexcitatory area. Microinjection of AVP into the nRVL in anesthetized rats produced a large dose-related increase in AP different from control at a dose of 1 pmol or higher. AVP injected intravenously elevated AP only at significantly higher doses. Microinjections of AVP into the nucleus tractus solitarii (NTS) had a smaller effect whereas into the caudal ventrolateral medulla exerted no effect on AP. Bilateral microinjections of an AVP antagonist, d(CH2)5[Tyr(Me)2]AVP into the nRVL produced no change in AP but blocked the increase produced by subsequent injections of AVP. An acute hemorrhage produced by withdrawal of 2 ml of blood from the femoral vein did not alter AP. However, bilateral microinjections of the AVP antagonist into the nRVL 5 min after hemorrhage decreased AP. In contrast, the AVP-antagonist injected intravenously after hemorrhage had no effect on AP. Our data suggest that under conditions demanding increased sympathetic drive to maintain AP, such as hemorrhage, a functional AVP receptor mechanism via terminals in the nRVL may be activated to restore normal levels of AP.
Assuntos
Arginina Vasopressina/análise , Pressão Sanguínea , Encéfalo/fisiologia , Bulbo/fisiologia , Neurônios/fisiologia , Animais , Arginina Vasopressina/administração & dosagem , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/farmacologia , Arginina Vasopressina/fisiologia , Transporte Axonal , Axônios/fisiologia , Axônios/ultraestrutura , Pressão Sanguínea/efeitos dos fármacos , Imunofluorescência , Hemorragia/fisiopatologia , Masculino , Bulbo/citologia , Bulbo/ultraestrutura , Microinjeções , Neurônios/citologia , Neurônios/ultraestrutura , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Sinapses/fisiologia , Sinapses/ultraestruturaRESUMO
La oportuna evacuación del líquido alveolar, la liberación del surfactante y el inicio de movimientos respiratorios son procesos claves para una adecuada adaptación del feto a la vida extrauterina. La arginina-vasopresina fetal aumenta al momento del parto e inhibe la secreción del líquido pulmonar por medio de un mecanismo aún no dilucidado. El objetivo de este trabajo fue estudiar el mecanismo por medio del cual este péptido disminuye la secreción de líquido pulmonar en el feto. Se utilizaron fetos de oveja crónicamente cateterizados e infundidos ya sea con arginina-vasopresina agonista V2 o antagonista V1. Se midió el flujo de líquido pulmonar durante cada período basal y de infusión. La arginina vasopresina disminuyó significativamente la secreción de líquido pulmonar al igual que el antagonista V1, efecto que fue más marcado al infundir ambos péptidos juntos. El agonista V2 en cambio no produjo cambios significativos en el flujo de líquido pulmonar. Nosotros concluimos que la arginina vasopresina disminuye significativamente la secreción de líquido pulmonar por medio de un mecanismo distinto a la activación de sus receptores conocidos V1 y V2 y postulamos la existencia de otro receptor ( o receptores) para la arginina-vasopresina activo durante la vida fetal
Assuntos
Animais , Arginina Vasopressina/administração & dosagem , Feto/efeitos dos fármacos , Traqueia , Ovinos , TraqueiaRESUMO
The present study was performed to investigate the effect of treatment with furosemide on the pressor response induced by intracerebroventricular (i.c.v.) injections of cholinergic (carbachol) and adrenergic (norepinephrine) agonists, angiotensin II (ANGII) and hypertonic saline (HS, 2 M NaCl). The changes induced by furosemide treatment on the pressor response to intravenous (i.v.) norepinephrine, ANGII and arginine vasopressin (AVP) were also studied. Rats with a stainless-steel cannula implanted into the lateral ventricle (LV) were used. Two injections of furosemide (30 mg/kg b.wt. each) were performed 12 and 1 h before the experiments. Treatment with furosemide reduced the pressor response induced by carbachol, norepinephrine and ANGII i.c.v., but no change was observed in the pressor response to i.c.v. 2 M NaCl. The pressor response to i.v. ANGII and norepinephrine, but not AVP, was also reduced after treatment with furosemide. These results show that the treatment with furosemide impairs the pressor responses induced by central or peripheral administration of adrenergic agonist or ANGII, as well as those induced by central cholinergic activation. The results suggest that the treatment with furosemide impairs central and peripheral pressor responses mediated by sympathetic activation and ANGII, but not those produced by AVP.
Assuntos
Angiotensina II/antagonistas & inibidores , Arginina Vasopressina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Carbacol/antagonistas & inibidores , Furosemida/farmacologia , Norepinefrina/antagonistas & inibidores , Solução Salina Hipertônica/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Arginina Vasopressina/administração & dosagem , Carbacol/administração & dosagem , Injeções Intravenosas , Injeções Intraventriculares , Masculino , Norepinefrina/administração & dosagem , Ratos , Solução Salina Hipertônica/administração & dosagemRESUMO
This study demonstrates that somatostatin (SRIF), an endogenous peptide in vestibular nuclei and cerebellum, can produce both a dose-dependent death of Purkinje cells in distinct sagittal regions of cerebellar cortex and vascular infarcts centered selectively in the inferior vestibular nucleus. Alert, adult male rats were given a 5 microliters intracerebroventricular (i.c.v.) bolus of either SRIF alone (20 or 40 micrograms) or a combined dose of SRIF plus either arginine-vasopressin (AVP, 1 micrograms) or an AVP V1 antagonist, (1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)-tyrosine)-arginine 8-vasopressin (mcAVP, 1 micrograms), through an implanted cannula. After a 4-5 day survival, the brains were stained with the cupric-silver selective degeneration method. Two types of dose-dependent lesions were observed in the cerebellar and vestibular nuclei of these animals: degeneration of Purkinje cell responses in the cerebellar cortex and vascular infarcts in vestibular nuclei. These toxic responses were unaffected by application of AVP or mcAVP; hence, they can be attributed to actions of SRIF. The distribution of Purkinje cell degeneration varied with the SRIF dose in different cerebellar regions. Purkinje cell responses in lobules I-III were equivalent at both SRIF doses, and degeneration in the copula pyramis, paraflocculus and paramedian lobule emerged at the higher SRIF dose. Purkinje cells in the medial aspect of lobules IX-X had an intermediate sensitivity to SRIF intoxication. Degenerating Purkinje cells tended to be arranged in parasagittal bands in each region, suggesting parasagittal zonal variations in susceptibility to SRIF intoxication. By contrast, infarctions in the vestibular nuclei only appeared at the higher SRIF dose. These infarcts could be unilateral or bilateral and always involved the inferior vestibular nucleus at the level of the caudal margin of the acoustic tubercle; they often extended into the medial and lateral vestibular nuclei. The infarcts had a necrotic core that was infiltrated by non-neuronal elements. Thus, they appear to reflect a direct or neurally-mediated vascular response to the peptide.