Intestinal glandular inclusions (glandular choristoma) in the mesenteric lymph node of a goat.

A glandular choristoma found in the mesenteric lymph node of a goat would appear to represent the first reported case of non-neoplastic glandular inclusions in domestic animals. The origin of this type of lesion may be difficult to determine, but in the present case cytokeratin expression patterns suggested that the inclusions had an intestinal origin.

Adrenalectomy reduces atrial natriuretic peptide stimulated guanylate cyclase activity in rat paraventricular nucleus.

Atrial natriuretic peptide (ANP) or an Atriopeptin III analog (PL 058) stimulated cGMP formation in the membrane fraction of rat olfactory bulb, median eminence and paraventricular nucleus, in a dose-dependent manner. The effect of the Atriopeptin III analog was 20-40% greater than that of ANP. Bilateral adrenalectomy, with or without mineralo- or glucocorticoid-replacement, on ANP-stimulated cGMP formation was investigated in rat paraventricular nucleus. 11 days after bilateral adrenalectomy a reduced responsiveness to ANP- or PL 058-induced cGMP production was observed. This effect was prevented by deoxycorticosterone, but not by dexamethasone administration. Our results further support the presence of guanylate cyclase-coupled ANP receptors in brain localized target sites; and they provide evidence suggesting that guanylate cyclase-linked ANP binding sites in the PVN are susceptible to regulatory changes after adrenalectomy-induced activation of the hypothalamus-hypophyso-adrenocortical system.

Brain natriuretic peptide stimulates particulate guanylate cyclase activity in selected areas of the rat brain.

The effect of porcine brain natriuretic peptide (pBNP) on cyclic guanosine monophosphate (cGMP) production was investigated in localized rat brain areas by radioimmunoassay procedure. Porcine BNP activated particulate guanylate cyclase in the median eminence, subfornical organ, choroid plexus, olfactory bulb, paraventricular nucleus and pineal gland in a concentration-dependent fashion and its action was comparable to that of rat atrial natriuretic peptide (alpha-ANP), with ED50 values ranging from 5 to 7 x 10(-7) M for both peptides. Our results suggest that the activation of a specific receptor coupled to the guanylate cyclase system and the subsequent elevation of cGMP levels constitutes the common mechanism of the central action of BNP and ANP.

Endothelin-3 stimulates phosphoinositide hydrolysis in the subfornical organ and median eminence of the rat brain.

The effect of Endothelin-3 on phosphoinositide turnover was studied in two brain structures, the subfornical organ and median eminence. ET-3 increased inositol monophosphate accumulation in the range 1 nM to 2 microM. Basal and stimulated InsP1 accumulation increased linearly during 1 h. The PI response elicited by ET-3 was dependent on the presence of extracellular Ca++. Removal of extracellular Ca++ or addition of Cd++ resulted in a marked decrease in ET-3-stimulated InsP1 accumulation. On the contrary, phosphoinositide hydrolysis was not changed by the calcium channel blockers nifedipine or amlodipine; however, it was decreased by amiloride, a Na+/H+ antiporter or Na+/Ca++ exchange blocker. ET-3 induced PI breakdown was inhibited in, a dose-dependent manner, by neomycin, an inhibitor of phospholipase C. These findings further support the hypothesis that stimulation of PI turnover constitutes one of the signalling pathways of ET-3 in the central nervous system, possibly through the stimulation of a specific receptor coupled to phospholipase C.

Rat atrial natriuretic peptide (99-126) stimulates guanylate cyclase activity in rat subfornical organ and choroid plexus.

The effect of rat atrial natriuretic peptide (99-126) (rANP) on cyclic guanosine 3',5'-monophosphate production was investigated in two brain areas, the subfornical organ and the choroid plexus. rANP activated guanylate cyclase in crude homogenates of rat subfornical organ and choroid plexus in concentration and time dependent fashions. A 2-fold stimulation of the enzyme was obtained with 100 nM rANP and a half-maximal stimulation with a 10 nM dose. Our results further support the hypothesis that cGMP mediates the central action of ANP through the activation of specific receptors in localized target sites such as the subfornical organ and choroid plexus.

Angiotensin II receptor subtypes and phosphoinositide hydrolysis in rat adrenal medulla.

Angiotensin II (ANG) receptor subtypes were characterized by quantitative autoradiography after incubation with the ANG agonist [124I]Sar1-ANG in rat adrenal medulla. ANG receptors are highly localized in adrenal medulla. Specific binding was displaced by 4% and by 95% with the AT, receptor blocker losartan and the AT2 receptor competitor CGP 42112A, respectively. Analysis of competition curves indicated relative binding potencies for the AT2 population of CGP 42112A>PD 123319> PD 123177. ANG stimulated +-nositol phosphate formation in a dose-dependent manner in rat adrenal medulla. Losartan at concentrations of 10(-9) to 10(-5) M antagonized the effect of ANG, whereas PD 123177 or PD 123319 had no antagonistic action. However, at a higher concentration (10(-5) M) PD 123177 or PD 123319 potentiated the effect of ANG on InsP1-accumulation. In the presence of PD 123319 (10(-5) M) ANG dose-response curve was shifted to the left with no change in the maximal effect. This affect was blocked by the addition of losartan (10(-5) M). On the contrary, the addition of CGP 42112A (10(-6) M) inhibited ANG-induced increase in InsP1-accumulation. On the other hand, ANG and CGP 42112A reduced basal cyclic GMP formation, this effect was partially reverted by sodium orthovanadate, a phosphotyrosine phosphatase inhibitor. Our results further demonstrate the presence of two ANG receptor subtypes in adrenal medulla: ANG binding to AT, receptor stimulates inositol phospholipid metabolism, whereas ANG binding to AT2 receptors decreases both inositol phosphate production and cGMP formation.

Role of endothelin in stress-induced hypertension.

In this study we investigated the role of endogenous endothelin in the cardiovascular response to acute stress, ie mild footshocks in conscious rats. Footshock-stress significantly increased mean arterial pressure and heart rate (P < 0.05). Peripheral or intracerebroventricular (IVT) administration of BQ 788, a selective antagonist of ET(B) receptor, did not alter pressor response to footshocks. Intraperitoneal injections of BQ 123 (1 mg/kg), a selective antagonist of the ET(A)-receptor, had a tendency to decrease, while BQ 123 (203 ng/5 microl) IVT administration significantly reduced the pressor response to footshocks (-12 mm Hg, P < 0.001). Neither ET(A) nor ET(B) antagonists, when injected centrally or peripherally, altered basal blood pressure or heart rate. Our results may indicate a role of brain endothelin in the sympathetic mediated cardiovascular response to stress, via stimulation of ET(A) receptor.

Vasoactive intestinal peptide (VIP) binding to solubilized material from rat liver plasma membranes.

A non-ionic detergent such as Lubrol-PX extracts in soluble form the VIP-binding structures of rat liver plasma membranes. Detergent-solubilized proteins bind specifically [125I]VIP and the complex tracer-protein is identified by the use of Sepharose 6B columns. The interaction is only possible in the absence of detergent (below 0.001%) and is inhibited by native peptide. A molecular weight of about 80,000 was estimated for VIP-binding proteins by reference to a series of globular markers of proteins. Binding to VIP soluble proteins is specific and dependent on time as studied by the Hummel and Dreyer (Biochim. Biophys. Acta 63:530-532, 1962) assay.

Endothelin ETA receptors subtype mediates phosphoinositide hydrolysis in adrenal medulla.

We investigated the effect of endothelins (ETs) on receptor-mediated phosphoinositide turnover in whole adrenal medulla. Endothelin -1, -2, -3 increased phosphoinositide (PI) turnover by 30% in whole adrenal medulla prelabeled with (3H)myoinositol. ET-stimulation of PI hydrolysis was almost completely dependent on the presence of the extracellular calcium since its chelation resulted in a blockade of ETs induced InsP1 accumulation. Addition of cadmium increased basal and ETs-stimulated InsP1 accumulation. ETs induced InsP1 accumulation was inhibited by BQ 123, a selective antagonist of the ETA receptor, while BQ 788, a selective antagonist of the ETB receptor, was ineffective. The selective agonist at the endothelin ETB receptor, IRL 1620, was ineffective to induce changes in inositide metabolism. Our data indicate that stimulation of PI turnover constitutes one of the signalling pathways of ETs in rat adrenal medulla and that this action is mediated through ETA receptor activation. These results suggest that endothelin could play a role in the regulation of adrenal medulla function.

[The female sex and mortality after acute myocardial infarct]. / Sexo femenino y mortalidad tras infarto agudo de miocardio.

INTRODUCTION: To study the possible influence of gender on in-hospital mortality in patients suffering acute myocardial infarction. PATIENTS AND METHODS: We analyzed 1,951 consecutive patients admitted to our Coronary Unit between January 1986 and December 1991 with this diagnosis and with a delay of no more than 24 hours prior to admission. RESULTS: In-hospital mortality was 12.8% in the 1,603 males and 25.6% in the 348 females (p < 0.001). Age, previous history of: not smoking, diabetes, heart failure, stable angina, myocardial infarction, stroke, right branch block, atrial fibrillation, and treatment with digoxin were variables significantly associated with greater mortality (p < 0.05) as well as the localization of the infarction, the Forrester grade and/or presence of atrioventricular block on admission and not treatment with intravenous fibrinolytics and beta-blockers. Multivariate analysis of variables associated with mortality (selection criterion for variable entry p < 0.20) shows that age, gender, previous angina, situation and extension of the infarction determined by ECG and Forrester on admission are independent predictors of in-hospital mortality. CONCLUSIONS: Gender is an independent predictor of in-hospital mortality in acute myocardial infarction (female/male odds ratio = 1.63).

Actividad de las enzimas antioxidantesen el riñon de la rata con preeclampsia experimental / Rat kidney antioxidant enzyme activities in experimental preeclampsia

La preeclampsia (PE) es un trastorno multisistémico del embarazo caracterizado por hipertensión, proteinuria y edema. La PE se asocia con la disfunción endotelial, el estrés oxidativo y con la disminución de la actividad de la sintasa del óxido nítrico (SON) endotelial. Los mecanismos de la vasodilatación asociada al embarazo normal sugieren que el óxido nítrico (NO) es el más importante mediador en la reducción de la resistencia vascular, mientras que en la PE la respuesta dilatadora dependiente de endotelio y mediada por el NO se encuentra reducida. Se ha demostrado que la inhibición de la síntesis del NO mediante la administración crónica de LNAME en ratas preñadas, resulta en un modelo animal que ocasiona un síndrome similar a la PE, el cual cursa con hipertensión, proteinuria, trombocitopenia y retardo de crecimiento intrauterino. Con el fin de caracterizar las alteraciones renales que ocurren durante la PE, empleamos este modelo animal de preeclampsia inducido por la inhibición de la SON, en ratas de 13 días de gestación. Se cuantifico la posible alteración en la actividad de las enzimas antioxidantes como la catalasa (CAT), superoxido dismutasa (SOD) y glutatión peroxidasa (GPx), así como la SON renal. El tratamiento crónicocon L-NAME en ratas preñadas incrementó la PAM (+20mmHg), produjo proteinuria, sin embargo no altero significativamente el número y el peso de los fetos. El estudio histológico de los riñones de animales pre-eclámpticos mostró que los mismos presentan tumefacción turbia de epitelios tubulares, focos hemorrágicos y congestión de capilares glomerulares. El tratamiento crónico con L-NAME en las ratas preñadas redujo la actividad de las tres enzimas antioxidantes evaluadasy de la SON renal. Estos hallazgos sugieren que la PE experimental cursa con alteración renal asociada con la reducciónde la actividad antioxidante y la inhibición de la SON.

Preeclampsia (PE) is a multisystem disorder of pregnancy characterized by hypertension, proteinuria and edema. PE is associated with endothelial dysfunction, oxidative stress and decreased endothelial nitric oxide synthase activity. The mechanisms of normal pregnancy-associated vasodilation suggest that nitric oxide (NO) is the most important mediator for the reduction of vascular resistance. Many studies demonstrat ereduction of endothelium-dependent dilator response mediated by NO in PE. Inhibition of NO synthesis is an animal model which results in a PE-like syndrome, hypertension, proteinuria, thrombocytopenia and intrauterine growth retardation. In order to assess the possible renal alteration in this animal model of preeclampsia induced by chronic administration of L-NAME, we determined the antioxidant enzymes activities (catalase, superoxide dismutase and gluthation peroxidase) and nitric oxide sinthase in the rat kidney. Chronic L-NAME treatment in pregnant rats increased MAP (+20mm Hg), produced proteinuria and did not change the number and weight of fetuses. Histological examination of the kidneys showed cloudy swelling PE tubular epithelia, hemorrhagic fociand congestion of glomerular capillaries. In addition, L-NAME treatment reduced CAT, SOD, GPx and NOS activity in the kidney. These findings suggest that in experimental preeclampsia, renal alterations are associated with a reduction in the antioxidant enzyme and NOS activities.