RESUMEN
BACKGROUND: Predicting bleeding after percutaneous kidney biopsy (PKB) is difficult. The value of Platelet Function Analyzer-100 (PFA-100) is not studied in this setting. METHODS: We undertook a prospective study of PFA-100 collagen/epinephrine (CEPI) and collagen/adenosine diphosphate (CADP) closure times among 56 participants (35 males and 21 females) undergoing PKB under real-time ultrasound (US) visualization at a tertiary teaching hospital. We collected data on age, sex, weight, height, blood pressure (BP), serum creatinine, random urine protein/creatinine ratio, electrolytes, PT/PTT, complete blood count, administration of desmopressin acetate and renal biopsy characteristics. Major outcomes were hematoma formation on US, packed red blood (PRBC) transfusions and hematuria. Data were analyzed with SPSS 16. RESULTS: PFA-CEPI was abnormal in 5 (8.93%) and PFA-CADP abnormal in 8 (14.3%) participants. Post-biopsy hematoma formation on US was detected in 11 (19%) participants, 5 (8.9%) had macroscopic hematuria and 4 (7%) required PRBC transfusion. Bleeding events did not correlate with body mass index, baseline BP or with each other. Hematuria and US-observed hematomas did not appear to be clinically relevant. PRBC transfusions showed a significant association with elevated baseline BUN (p = 0.031), creatinine (p = 0.011) and the number of biopsy passes (p = 0.008). PFA-100 CEPI and CADP did not associate with any of the bleeding complications after PKB (p = NS). CONCLUSIONS: Measuring PFA-100 is unlikely to add to the care of patients undergoing routine PKB. ClinicalTrials.gov NCT00334204.
Asunto(s)
Biopsia/efectos adversos , Plaquetas/fisiología , Hematoma/diagnóstico , Hematuria/diagnóstico , Enfermedades Renales/patología , Pruebas de Función Plaquetaria/instrumentación , Adulto , Anciano , Biopsia/métodos , Diseño de Equipo , Femenino , Estudios de Seguimiento , Hematoma/sangre , Hematoma/etiología , Hematuria/sangre , Hematuria/etiología , Humanos , Enfermedades Renales/sangre , Enfermedades Renales/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Pronóstico , Estudios Prospectivos , Reproducibilidad de los Resultados , Factores de Tiempo , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND: Previous studies have shown that bleeding times have positive predictive values of only 5% for perioperative bleeding in unselected populations. Nevertheless, performing bleeding times prior to all renal biopsies is common in nephrology practice. METHODS: We report complications of 112 renal biopsies done at Walter Reed Army Medical Center (WRAMC) from 1996-99 performed without preceding bleeding times. Renal biopsies were done only on normotensive (<140/90) patients who had not recently been taking aspirin or non-steroidal anti-inflammatory agents, under real-time ultrasound guidance with automated 16 g (WRAMC) spring-loaded guns. High-risk patients (with serum creatinine > or = 3 mg/dl or creatinine clearance < or =30 cc/min by Cockroft-Gault formula, N=18, 16%) at WRAMC were treated with pre-renal biopsy estrogens or DDAVP. Factors were tested for their association with complications after renal biopsy using Chi Square testing for categorical variables and student's t-test for continuous variables. A stepwise logistic regression model was used to test for independent significance of factors. RESULTS: There were two cases each of gross hematuria and inadequate tissue (1.8% each). There were no transfusions or deaths. In univariate analysis, male gender and lower serum creatinine level at time of biopsy were significantly associated with increased risk of complications after biopsy. However, these factors were not significant in logistic regression analysis. CONCLUSION: This study suggests that the use of bleeding times does not significantly alter the major complication rates associated with percutaneous real-time ultrasound guided renal biopsy.
Asunto(s)
Biopsia con Aguja/efectos adversos , Riñón/diagnóstico por imagen , Riñón/patología , Hemorragia Posoperatoria/sangre , Hemorragia Posoperatoria/etiología , Adolescente , Adulto , Anciano , Biopsia con Aguja/métodos , Tiempo de Sangría , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hemorragia Posoperatoria/epidemiología , Estudios Retrospectivos , UltrasonografíaRESUMEN
ANG II has been implicated in neuroplastic processes via stimulation of inducible transcription factors (ITF) in the brain. In the present study, we investigated the effects of acute vs. repetitive once daily intracerebroventricular injections of ANG II for 7 days on the expression of ITF and constitutive transcription factor (CTF) and the AT1 receptor in the median preoptic area (MnPO), the subfornical organ (SFO), and the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). After repetitive injections, the expression of c-Fos declined by approximately 50% in MnPO, SFO, PVN, and SON compared with controls injected once. The desensitization of c-Fos occurred on the transcriptional level as shown in the SON by RT-PCR. Apart from a novel expression of c-Jun in the SON, the ITF c-Jun, JunB, JunD, and Krox-24 did not change after repetitive stimulation. Neither were the CTF, calcium response element binding protein, activating transcription factor 2, and serum response factor altered after repetitive vs. single injections of ANG II. The AT1 receptor was coexpressed with c-Fos/c-Jun. Immunohistochemical stainings suggest an increase in AT1-receptor number in MnPO, SFO, PVN, and SON on chronic stimulation compared with once-injected controls. These findings demonstrate that repetitive periventricular stimulation with ANG II essentially alters the expression of transcription factors compared with acute stimulation and suggest c-Fos and c-Jun as major intermediates of the AT1-receptor transcription.
Asunto(s)
Angiotensina II/farmacología , Encéfalo/fisiología , Proteínas de Drosophila , Genes fos/efectos de los fármacos , Receptores de Angiotensina/genética , Factor de Transcripción Activador 2 , Angiotensina II/administración & dosificación , Animales , Encéfalo/efectos de los fármacos , Ventrículos Cerebrales/efectos de los fármacos , Ventrículos Cerebrales/fisiología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas de Unión al ADN/metabolismo , Esquema de Medicación , Genes jun/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , Proteínas de la Membrana/metabolismo , Proteínas Nucleares/metabolismo , Especificidad de Órganos , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/fisiología , Área Preóptica/efectos de los fármacos , Área Preóptica/fisiología , Proteínas Proto-Oncogénicas c-fos/análisis , Proteínas Proto-Oncogénicas c-fos/genética , Ratas , Ratas Wistar , Receptor de Angiotensina Tipo 1 , Receptor de Angiotensina Tipo 2 , Receptores de Angiotensina/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Respuesta Sérica , Órgano Subfornical/efectos de los fármacos , Órgano Subfornical/fisiología , Núcleo Supraóptico/efectos de los fármacos , Núcleo Supraóptico/fisiología , Factores de Tiempo , Factores de Transcripción/metabolismoRESUMEN
Health maintenance includes secondary prevention through cancer screening. There are no established guidelines for cancer screening patients with end-stage renal disease (ESRD). Using an established method of estimating life expectancy, published literature on cancer screening, and information from databases on mortality and malignancy (US Renal Data System 1997 Annual Data Report and the SEER Cancer and Statistical Review, 1973-1994), a "real-time life expectancy calculator" was developed to guide the primary help provider in making informed decisions on the benefits of cancer screening in individual patients. Potential days of life saved by each screening method can be calculated using the difference in life expectancy per the DEALE (declining exponential approximation of life expectancy) method with and without cancer screening. Using two sets of assumptions (one to enhance any bias toward support for screening and one to limit this bias), a range of potential days of life saved with screening for breast and colon cancer can be calculated in individual patients with ESRD. In breast cancer, for example, a 50-year-old black woman with ESRD and multiple risk factors would have 41 to 291 potential days of life saved with screening. A 60-year-old white woman with ESRD and diabetes mellitus (DM) would have only 1 to 16 days of life saved. This life expectancy calculator can guide the primary health care provider in making clinical decisions concerning screening in the ESRD population. In addition to assisting in patient education, the calculator can be updated as new information becomes available regarding relative risk, treatment, and mortality.
Asunto(s)
Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Esperanza de Vida , Tamizaje Masivo/métodos , Neoplasias/diagnóstico , Neoplasias/mortalidad , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/etiología , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Modelos Teóricos , Neoplasias/etiologíaRESUMEN
In the present study, we investigated the expression pattern of the inducible transcription factors (ITF) c-Fos, c-Jun, JunB, JunD, and Krox-24 following intracerebroventricular injections of hyperosmolar saline (0.2, 0.3, and 0.6 M NaCl) and its mediation via angiotensin and/or muscarinic receptors. c-Fos, c-Jun, and Krox-24 were differentially expressed in organum vasculosum laminae terminalis, median preoptic area, subfornical organ (SFO), and paraventricular and supraoptic nuclei. Expression of c-Fos and c-Jun was inhibited by pretreatment with the angiotensin AT1 receptor antagonist losartan (10 and 20 nmol icv) following 0.20 and 0.30 M saline. Pretreatment with atropine (15 nmol icv) inhibited the 0.30 and 0.60 M NaCl-induced expression of c-Fos, c-Jun, and Krox-24 in all areas except the SFO. Coexpression of the ITF with vasopressin and oxytocin, the major effector peptides in osmoregulation, was demonstrated, implying the corresponding genes as putative target genes of the ITF. The results show a highly differentiated ITF expression pattern in the brain mediated by angiotensinergic and muscarinergic pathways, suggesting a finely tuned regulation of target genes.
Asunto(s)
Ventrículos Cerebrales/fisiología , Proteínas de Unión al ADN/biosíntesis , Hipotálamo/metabolismo , Proteínas Inmediatas-Precoces , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Proteínas Proto-Oncogénicas c-jun/biosíntesis , Receptores de Angiotensina/fisiología , Receptores Muscarínicos/fisiología , Solución Salina Hipertónica/farmacología , Factores de Transcripción/biosíntesis , Animales , Atropina/farmacología , Proteína 1 de la Respuesta de Crecimiento Precoz , Regulación de la Expresión Génica/efectos de los fármacos , Hipotálamo/efectos de los fármacos , Inyecciones Intraventriculares , Losartán/administración & dosificación , Losartán/farmacología , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Especificidad de Órganos , Oxitocina/biosíntesis , Núcleo Hipotalámico Paraventricular/metabolismo , Área Preóptica/metabolismo , Ratas , Ratas Wistar , Solución Salina Hipertónica/administración & dosificación , Núcleo Supraóptico/metabolismo , Vasopresinas/biosíntesis , Dedos de ZincRESUMEN
We studied the time course of expression of the inducible transcription factors (ITF) c-Fos, FosB, c-Jun, JunB, JunD, Krox-20 and Krox-24, induced by a single intracerebroventricular injection of angiotensin II, in the subfornical organ (SFO), median preoptic nucleus (MnPO) paraventricular nucleus (PVN) and supraoptic nucleus (SON). c-Fos and Krox-24 were expressed rapidly in neurons of all four areas but completely disappeared after 4 h. FosB showed a delayed but persistent expression between 4 h and 24 h in the MnPO and PVN. c-Jun was induced in the MnPO, SFO and PVN after 1.5 h and in the SON after 4 h. JunB was selectively expressed in the MnPO and SFO and the level of JunD did not change. The expression of the pre-existing transcription factors SRF, CREB and ATF-2 which contribute to the transcriptional control of jun, fos and krox genes, was not affected by Ang II. Thus, we could show for the first time that an acute stimulation of AT receptors results in continual changes in ITF expression over 24 h.
Asunto(s)
Angiotensina II/farmacología , Proteínas de Unión al ADN/biosíntesis , Hipotálamo/efectos de los fármacos , Proteínas Inmediatas-Precoces , Factor de Transcripción AP-1/biosíntesis , Factores de Transcripción/biosíntesis , Animales , Proteína 1 de la Respuesta de Crecimiento Precoz , Proteína 2 de la Respuesta de Crecimiento Precoz , Hipotálamo/metabolismo , Inyecciones Intraventriculares , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Área Preóptica/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Proteínas Proto-Oncogénicas c-jun/biosíntesis , Ratas , Ratas Wistar , Órgano Subfornical/efectos de los fármacos , Núcleo Supraóptico/efectos de los fármacos , Factores de TiempoRESUMEN
A stimulated brain renin-angiotensin system has been implicated in genetic hypertension. We compared the effects of an intracerebroventricular injection of angiotensin II (100 ng) on the expression of inducible transcription factors c-Fos, c-Jun, and Krox-24 in the brain of spontaneously hypertensive rats (SHR). in Wistar rats with nephrogenic hypertension induced by aortic banding, and in normotensive Wistar-Kyoto and Wistar rats immunohistochemically. Generally, the angiotensin II-induced transcription factor expression was strictly confined to four distinct forebrain areas: the subfornical organ, median preoptic area, paraventricular nucleus, and supraoptic nucleus. In SHR, the angiotensin II-induced c-Fos and c-Jun expressions were significantly enhanced compared with those in normotensive control strains as well as in secondary hypertensive Wistar rats. Krox-24 expression in the subfornical organ, median preoptic area, and paraventricular nucleus of SHR was also significantly increased compared with that in all control strains. In the supraoptic nucleus, significant differences could be discriminated between SHR and secondary hypertensive Wistar rats. Injection of isotonic saline or arginine vasopressin (100 ng) as controls did not induce any expression of c-Fos, c-Jun, or Krox-24. Our findings demonstrate an enhanced sensitivity of SHR to angiotensin II-induced transcription factor expression in distinct brain areas involved in central blood pressure and osmotic control that is independent of blood pressure.
Asunto(s)
Angiotensina II/farmacología , Proteínas de Unión al ADN/metabolismo , Hipertensión/metabolismo , Proteínas Inmediatas-Precoces , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-jun/metabolismo , Factores de Transcripción/metabolismo , Antagonistas de Receptores de Angiotensina , Animales , Arginina Vasopresina/farmacología , Compuestos de Bifenilo/farmacología , Presión Sanguínea , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Proteínas de Unión al ADN/efectos de los fármacos , Proteína 1 de la Respuesta de Crecimiento Precoz , Imidazoles/farmacología , Inmunohistoquímica , Inyecciones Intraventriculares , Losartán , Proteínas Proto-Oncogénicas c-fos/efectos de los fármacos , Proteínas Proto-Oncogénicas c-jun/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Ratas Wistar , Tetrazoles/farmacología , Factores de Transcripción/efectos de los fármacosRESUMEN
The effects of intracerebroventricular (i.c.v.) injections of angiotensin II (Ang II) on the expression of inducible transcription factors (ITF) (c-Fos, FosB, c-Jun, JunB, JunD, Krox-20 and Krox-24) in the brain of conscious rats were assessed immunohistochemically using polyclonal antisera. Ang II (1, 10, 100 ng) induced after 90 min a dose-dependent expression of c-Fos, FosB, c-Jun, JunB and Krox-24, which was confined to four specific brain areas, namely the subfornical organ (SFO), median preoptic area (MnPO), paraventricular nucleus (PVN) and supraoptic nucleus (SON). In the above-mentioned regions, JunD exhibited a high basal staining which was not visibly altered by Ang II. Krox 20 was not induced by AnG II. FosB was only induced 4 h after i.c.v. injection of 100 ng Ang II in the MnPO and PVN. The Ang II-AT1 receptor antagonist, losartan, applied i.c.v. 5 min prior to Ang II (100 ng, i.c.v.) prevented the Ang II-induced ITF expression. In spontaneously hypertensive rats (SHR) but not in Wistar rats with nephrogenic hypertension due to aortic banding (WIab), the Ang II-induced expression of c-Fos, and c-Jun was enhanced in all four areas when compared to normotensive Wistar Kyoto (WKY)- and Wistar (WI) rats. The Ang II-induced expression of Krox-24 in the SFO, MnPO and PVN in SHR was also significantly increased when compared to WKY, WI and WIab rats. Our data demonstrate that a stimulation of periventricular Ang II-AT1 receptors induces a temporally and spatially highly differentiated expression pattern of ITFs restricted to four distinct regions of the forebrain involved in blood pressure regulation and body fluid homeostasis. The points to a strictly regulated expression of target genes in the respective regions. The enhanced Ang II-induced expression of ITFs in SHR compared to normotensive controls is not due to elevated blood pressure itself, since it was not observed in secondary hypertensive rats WIab. Thus, the increased sensitivity to Ang II in SHR appears to be genetically determined. The target genes regulated by Ang II-induced ITFs will have to be identified.
Asunto(s)
Angiotensina II/fisiología , Encéfalo/metabolismo , Regulación de la Expresión Génica , Proto-Oncogenes , Factores de Transcripción/biosíntesis , Angiotensina II/administración & dosificación , Angiotensina II/farmacología , Animales , Encéfalo/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Regulación de la Expresión Génica/inmunología , Inyecciones Intraventriculares , Proto-Oncogenes/efectos de los fármacos , Proto-Oncogenes/genética , Proto-Oncogenes/inmunología , Ratas , Factores de Transcripción/genética , Dedos de Zinc/efectos de los fármacos , Dedos de Zinc/genética , Dedos de Zinc/inmunologíaRESUMEN
The effects of intravenous fluids on hematocrit are debated. We sought to determine whether maintenance or bolus fluid therapy causes a significant change in the hematocrit and other hematologic parameters included in the complete blood count. Nine subjects completed a randomized three-period crossover designed trial in which they were given no fluid, maintenance fluid, or a bolus of fluid followed by maintenance fluid. We measured complete blood counts at baseline, 1 hour, 4 hours, and 8 hours. In the bolus fluid trial, the hemoglobin and hematocrit values (mean +/- SEM) decreased by a maximum of 1.5 +/- 0.1 g/dL and 4.1 +/- 0.3% at 1 hour. There was no difference in hemoglobin or hematocrit during the no fluid or maintenance fluid treatments. No significant changes occurred in white blood cell or platelet counts. We demonstrated that maintenance fluid infusions do not significantly after the complete blood count. Saline bolus is associated with a significant decrease in hemoglobin and hematocrit, but these parameters trend toward baseline over time.
Asunto(s)
Fluidoterapia , Hematócrito , Hemodilución , Hemoglobinas/análisis , Equilibrio Hidroelectrolítico , Adulto , Análisis de Varianza , Recuento de Células Sanguíneas , Estudios Cruzados , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Cloruro de Sodio/administración & dosificaciónRESUMEN
We have investigated the effects of intracerebroventricular injections of angiotensin II in conscious rats on the expression of c-fos messenger RNA (mRNA) in the caudate nucleus, hypothalamus, midbrain and brainstem using semi-quantitative polymerase chain reaction and Northern Blots. RNA analysis revealed the presence of c-fos transcripts in the midbrain and brainstem following icv injections of ANG II. ANG II (1, 10, 100 ng) induced a substantial increase in c-fos mRNA in the brainstem which was significant after 10 ng ANG II, and less after 100 ng. This effect was time-dependent being detectable within 15 minutes and maximal after 60 minutes. This ANG II-induced c-fos mRNA expression was totally inhibited by icv pretreatment with the ANG II-AT1 receptor antagonist, losartan. Our data show for the first time that stimulation of central periventricular AT1 receptors induces the expression of c-fos mRNA in the brain. Thus, ANG II, in addition to its short-term regulatory actions, can participate through transcription factors in neuroplastic processes.
Asunto(s)
Angiotensina II/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Genes fos/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Angiotensina II/administración & dosificación , Antagonistas de Receptores de Angiotensina , Animales , Compuestos de Bifenilo/farmacología , Tronco Encefálico/metabolismo , ADN Complementario/genética , Expresión Génica/efectos de los fármacos , Imidazoles/farmacología , Inyecciones Intraventriculares , Losartán , Masculino , Mesencéfalo/metabolismo , Reacción en Cadena de la Polimerasa , Ratas , Ratas Wistar , Tetrazoles/farmacologíaRESUMEN
We investigated the effects of intracerebroventricular injection of angiotensin II on neuronal immediate early gene-encoded protein synthesis in the brain of conscious rats. The expression of seven immediate early gene-encoded transcription factors (c-Fos, FosB, c-Jun, JunB, JunD, Krox-20 (Egr-2) and Krox-24 (NGFI-A, Egr-1, Zif/268) was assessed simultaneously. Angiotensin II (1, 10, 100 ng) induced a dose-dependent expression of c-Fos and Krox-24 in the subfornical organ, the median preoptic area and in the paraventricular nucleus and supraoptic nucleus of the hypothalamus, regions known to be involved in the central osmoregulatory and neuroendocrine actions of angiotensin II. FosB expression was induced four hours after icv injection of the highest dose of angiotensin II in the median preoptic area and paraventricular nucleus, c-Jun expression was restricted to the median preoptic area, subfornical organ and paraventricular nucleus, and JunB was only induced in the median preoptic area and subfornical organ. In these above mentioned regions, JunD exhibited a high basal staining, which was not visibly altered by angiotensin II. Krox-20 was not induced by angiotensin II. Intracerebroventricular injections of isotonic saline did not induce immediate early gene expression in any of the above brain areas. The angiotensin II-AT1 receptor antagonist, losartan, applied intracerebroventricular five minutes prior to angiotensin II, prevented the angiotensin II-induced immediate early gene protein expression. Losartan alone had no effects on immediate early gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Angiotensina II/farmacología , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-jun/genética , Transcripción Genética/genética , Animales , Relación Dosis-Respuesta a Droga , Expresión Génica , Genes Inmediatos-Precoces , Inyecciones Espinales , Masculino , Prosencéfalo/fisiología , Ratas , Ratas WistarRESUMEN
Substance P (SP) has been shown to stimulate the hydrolysis of inositol phospholipids in peripheral tissues and in the brain. In mammalian peripheral tissues, three tachykinin receptor subclasses, neurokinin 1 (NK1), neurokinin 2 (NK2) and neurokinin 3 (NK3), have been identified. The purpose of our study was to pharmacologically characterize the SP receptors in the hypothalamus using phosphoinositide breakdown as a functional response. SP, previously described as a NK1 agonist, and Neurokinin A (NKA), previously described as a NK2 agonist, stimulated phosphoinositide breakdown in the hypothalamus in a dose-dependent fashion, with SP being more potent than NKA. The NK2-selective antagonist L-659,877, at a dose of 10(-6) M, abolished the effect of SP (10(-8) M) without affecting basal phosphoinositide breakdown. However, this NK2-selective antagonist did not inhibit the NKA-induced stimulation in phosphoinositide metabolism. The NK1-selective antagonist L-668,169 stimulated phosphoinositide metabolism at a concentration of 10(-6) M, but not at 10(-8) M. This NK1-receptor antagonist did not significantly inhibit the effect of SP on phosphoinositide metabolism. Spantide II, another NK1-selective antagonist, also stimulated phosphoinositide metabolism at a dose of 10(-6) M. Like L-668,169, spantide II failed to inhibit the SP-induced stimulation of phosphoinositide metabolism, and even potentiated the response to SP.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Hipotálamo/metabolismo , Neuroquinina A/farmacología , Fosfatidilinositoles/metabolismo , Receptores de Neuroquinina-1/fisiología , Sustancia P/farmacología , Animales , Carbacol/farmacología , Relación Dosis-Respuesta a Droga , Hipotálamo/efectos de los fármacos , Técnicas In Vitro , Inositol/metabolismo , Masculino , Fragmentos de Péptidos/farmacología , Péptidos Cíclicos/farmacología , Ratas , Ratas Wistar , Receptores de Neuroquinina-1/efectos de los fármacos , Sustancia P/análogos & derivados , Taquicininas/antagonistas & inhibidoresRESUMEN
Ramipril, a converting enzyme inhibitor, was first studied in rats with aortic stenosis, an experimental model of reno-vascular hypertension. In this study, ramipril has an antihypertrophic cardiac effect, independently to its hypotensive effect. The co-administration of Hoe 140, a specific antagonist of bradykinin receptors blocked totally the effect of ramipril on blood pressure, cardiac hypertrophy and on concentration of cGMP. These effects can therefore be explained by an accumulation of bradykinins. Furthermore, we investigated the preventing effects of ramipril on left ventricular hypertrophy, on growth of cardiac capillaries using SHR rats, treated in utero and during the 20 weeks following birth with two doses: a relatively high dose (1 mg/kg/day) and a low dose (0.01 mg/kg/day). Animals treated with a low dose of ramipril presented a high blood pressure similar to that observed in the control group. At the end of the treatment, the converting enzyme activity was inhibited in both groups. An increase in the growth of cardiac capillaries and of the cardiac concentration of glycogen and a decrease in the cardiac concentration of citric acid was observed in both groups. The ventricular weight decreased only in the high dose treatment group. This results demonstrated that early treatment with converting enzyme inhibitor even with a low dose which was unable to prevent the development of hypertension and of left ventricular hypertrophy. We could therefore draw a hypothesis of an accumulation of bradykinin due to the converting enzyme inhibitor which could explain in part this effect through an improvement of cardiac metabolism.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Presión Sanguínea/efectos de los fármacos , Bradiquinina/fisiología , Compuestos Bicíclicos con Puentes/farmacología , Hipertensión Renovascular/fisiopatología , Oligopéptidos/farmacología , Animales , Ramipril , Ratas , Ratas Endogámicas SHR , Receptores de Bradiquinina , Receptores de Neurotransmisores/antagonistas & inhibidoresRESUMEN
Previous in vivo and in vitro studies have demonstrated that exposure of the brain to arginine vasopressin (AVP) can potentiate various responses to a second central challenge with AVP. To determine whether this sensitization is mediated by changes at the receptor level, we investigated the effects of AVP on the phosphoinositide metabolism in septal slices prepared from rats centrally pretreated with saline or AVP. Addition of vasopressin (10(-7) M, 10(-6) M) to septal slices from saline-pretreated rats failed to elicit a significant stimulation of inositol-1-phosphate (IP1). In contrast, AVP (10(-7) M) significantly stimulated IP1 release in septal slices prepared from rats pretreated intracerebroventricularly (i.c.v.) 24 h earlier with 10 or 100 ng AVP. Pretreatment with the same i.c.v. doses of AVP also induced a significant enhancement of the carbachol-induced stimulation of IP1 release, but i.e.v. pretreatment with carbachol did not stimulate the IP1 release in response to AVP. Our results suggest that a novel facilitation of phosphoinositide metabolism can be induced by central AVP pretreatment.
Asunto(s)
Arginina Vasopresina/farmacología , Encéfalo/metabolismo , Ventrículos Cerebrales/fisiología , Fosfatos de Inositol/metabolismo , Fosfatidilinositoles/metabolismo , Animales , Arginina Vasopresina/administración & dosificación , Encéfalo/efectos de los fármacos , Carbacol/farmacología , Ventrículos Cerebrales/efectos de los fármacos , Técnicas In Vitro , Inyecciones Intraventriculares , Inositol/metabolismo , Cinética , Masculino , Ratas , Ratas Endogámicas , Valores de Referencia , TritioRESUMEN
Arginine vasopressin (AVP) injected intracerebroventricularly (i.c.v.) in the nanogram range elicits increases in mean arterial blood pressure (MAP), heart rate (HR) and efferent sympathetic nerve activity (SpNA) via central V1 AVP receptor stimulation. In this study in conscious rats we investigated, whether the cardiovascular and sympathetic responses can be augmented by repeated central applications of AVP, as has been previously shown for the convulsive responses to higher i.c.v. doses of the peptide. The AVP-induced pressor (0.1 and 1.0 ng) and the SpNA (0.1 ng) responses were significantly enhanced by a second AVP challenge 24 h after the first injection. With higher doses of the peptide (3 ng), the blood pressure responses were not different between two subsequent injections, but barrel rotation occurred in 21% of the animals upon the second challenge. The pressor responses to a threshold i.c.v. dose of 1 ng angiotensin II (ANG II) were not enhanced upon a second ANG II challenge. Our results demonstrate that AVP, unlike ANG II, can sensitize central mechanisms leading to increased MAP and SpNA responses.
Asunto(s)
Fibras Adrenérgicas/efectos de los fármacos , Arginina Vasopresina/farmacología , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Fibras Adrenérgicas/fisiología , Animales , Relación Dosis-Respuesta a Droga , Inyecciones Intraventriculares , Masculino , Ratas , Ratas EndogámicasRESUMEN
Ethanol's post-training facilitation of memory was examined using a latent learning paradigm known as the "water-finding task." Rats were assigned to one of two ethanol groups (E0.75 g/kg or E1.5 g/kg) or to a control group (saline) and individually placed in a novel open field containing a drinking tube. Following this exposure, subjects were immediately administered intraperitoneal (IP) injections of either the saline or ethanol and 48 hours later, re-introduced to the field. Initial latencies to contact the tube each time were recorded. A linear regression analysis of trial 2 latencies regressed onto trial 1 latencies indicated a statistically significant effect of ethanol on the relation between initial and subsequent latencies. Though the control rats' trial 2 latencies were completely random with respect to their previous speeds (rSAL = -0.07), the ethanol rats' trial 2 latencies were positively correlated with initial speeds (rE0.75 = 0.35, rE1.5 = 0.67). These results suggest that under conditions of post-training ethanol, trial 2 behavior is more similar to, or controlled by, trial 1 behavior and are consistent with the argument that, under certain training and testing contexts, ethanol can come to exert control over a response's recurrence.
Asunto(s)
Etanol/farmacología , Aprendizaje/efectos de los fármacos , Memoria/efectos de los fármacos , Análisis de Varianza , Animales , Masculino , Ratas , Ratas Endogámicas , Tiempo de Reacción/efectos de los fármacosRESUMEN
Several studies have suggested that arginine vasopressin (AVP) may act centrally as a neurohormone or neuromodulator to produce electrophysiological and behavioral effects. However, there are few reports of EEG effects of AVP in unanesthetized, behaving animals. In the present study the EEG effects of "behaviorally relevant" subcutaneous (SC) doses of AVP (6 micrograms/kg) known to raise blood pressure were compared to "behaviorally relevant" intracerebroventricular (ICV) doses (0.1-1.0 ng) and multiple "toxic" ICV doses (1.0 microgram) of AVP. Central injections of toxic doses of AVP produced behavioral arrest, bodily barrel rolling, and EEG slowing, but did not induce electrographic signs of seizure activity. Comparison of the spectral characteristics of the EEG revealed some similarities in the distribution of power between SC and the 1.0 ng ICV dose; whereas ICV doses of 0.1 and 0.5 ng produced power distributions that were different from those seen following saline or SC doses of AVP. The similarities in EEG activity between SC injections and the 1.0 ng ICV dose suggest a common brain state may be induced by the two routes of administration in those dose ranges.
Asunto(s)
Arginina Vasopresina/farmacología , Encéfalo/efectos de los fármacos , Electroencefalografía , Animales , Arginina Vasopresina/administración & dosificación , Inyecciones Intraventriculares , Inyecciones Subcutáneas , Masculino , Ratas , Ratas Endogámicas , Convulsiones/inducido químicamenteRESUMEN
After training in two different passive avoidance tasks, the platform box of Ader and De Wied (1972) and the Jarvik box of Jarvik and Kopp (1967), rats injected with vasopressin immediately following the training trial showed a significant enhancement of retention 24 hours later. This vasopressin effect was reversed by high doses of the vasopressor antagonist, dPtyr(Me) AVP. These results support the hypothesis that the visceral afferent signals may be involved in the apparent memory-enhancing effects of AVP, but the high doses of antagonist required suggest that factors other than a simple reversal of the pressor effects of AVP may be important.
Asunto(s)
Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/farmacología , Reacción de Prevención/efectos de los fármacos , Animales , Arginina Vasopresina/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Masculino , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
Experiments were undertaken to determine the role of the septum on the afferent control of the milk ejection reflex in lactating rats. Massive septal lesions were produced by passing radio-frequency current through lesioning electrodes. Intramammary pressure recordings during suckling showed no significant alterations either in the frequency of milk ejections or in their amplitude and time course. Electrophysiological recordings of identified oxytocin-secreting neurones in supraoptic nuclei of septal-lesioned rats engaged in suckling showed that the pattern of background electrical activity and of the high frequency discharges at milk ejection were normal. The weight of litters from rats lesioned on the third day post-partum increased in a way parallel to that of control litters up to the fifteenth post-natal day. Electrical stimulation was applied bilaterally to the lateral septum in trains of long duration (20-55 min) at varying frequencies. Frequencies of 5 and 10 Hz interrupted the reflex during the period of stimulation. At 1 Hz, milk ejections were not interrupted but the intervals between successive milk ejections were significantly increased in comparison to the intervals before stimulation. Electrical stimulation applied to the septum in short trains of 1 or 3 min at 5 and 10 Hz significantly delayed the appearance of the subsequent milk ejection. At 1 Hz, no effect was observed. Septal stimulation at 1 Hz for 20 min or more did not significantly alter the electrocorticogram during the period of stimulation. Stimulation at 5 Hz for the same period of time always desynchronized the e.e.g. for several minutes after the cessation of stimulation. It is concluded that the septum is not essential for the onset and the maintenance of reflex milk ejections during lactation. The results suggest, however, that in the normal non-anaesthetized animal, septal activation could modulate the frequency of milk ejections.
Asunto(s)
Lactancia , Eyección Láctea , Tabique Pelúcido/fisiología , Potenciales de Acción , Animales , Peso Corporal , Estimulación Eléctrica , Femenino , Glándulas Mamarias Animales/fisiología , Oxitocina/metabolismo , Embarazo , Presión , Ratas , Tabique Pelúcido/lesiones , Núcleo Supraóptico/fisiología , Factores de TiempoRESUMEN
Extracellular recordings from neurones in the lateral septum were performed in urethane anaesthetised lactating rats to study the eventual role of the septum in the control of suckling-induced oxytocin release. The connections of these neurones with the supraoptic nucleus, which contains cells secreting oxytocin, were assessed electrophysiologically by single pulse stimulation of the ipsilateral supraoptic nucleus. The neurones were thus classified into four categories: antidromically activated, orthodromically activated or inhibited, and unresponsive neurones. One hundred septal neurones were recorded in animals not exposed to suckling. A second group of 40 cells were analysed during suckling and one or more reflex milk ejections. The mean firing rates of each category of septal neurone did not differ significantly during suckling from the values observed in the absence of suckling. During suckling, almost all the recorded septal cells showed no significant alteration in their level of firing in relation to milk ejections. Two neurones presented an activation in the period between two milk ejections that seemed related to arousal. One neurone was clearly inhibited at the time of milk ejection. Our observations suggest that the septum does not represent an essential component of the pathways necessary for the milk ejection reflex induced by suckling, although it could exert an inhibitory action modulating either the intervals between two successive milk ejections, or the amount of oxytocin released.