RESUMEN
The actions of a purified Helicobacter pylori lipopolysaccharide (3 mg x kg(-1), i.v.) on rat gastric antral and duodenal microvascular integrity (determined as radiolabelled albumin leakage) and the expression of the inducible nitric oxide (NO) synthase (iNOS; assessed by the citrulline assay) were investigated 4 h after challenge. Significant increases of albumin leakage and expression of iNOS in both antral and duodenal tissues were observed following challenge. Concurrent administration of the selective iNOS inhibitor, 1400W (N-(8-(aminomethyl)benzyl)-acetamidine; 0.2-1 mg x kg(-1), s.c.), with lipopolysaccharide, caused a dose-dependent attenuation of the gastric and duodenal albumin leakage. Thus, H. pylori lipopolysaccharide can initiate the expression of iNOS in the stomach and duodenum following systemic challenge, which can provoke gastroduodenal microvascular dysfunction.
Asunto(s)
Permeabilidad Capilar/efectos de los fármacos , Sistema Digestivo/efectos de los fármacos , Lipopolisacáridos/toxicidad , Óxido Nítrico Sintasa/metabolismo , Amidinas/farmacología , Animales , Bencilaminas/farmacología , Sistema Digestivo/irrigación sanguínea , Sistema Digestivo/patología , Relación Dosis-Respuesta a Droga , Duodeno/efectos de los fármacos , Duodeno/enzimología , Duodeno/patología , Inhibidores Enzimáticos/farmacología , Helicobacter pylori/química , Humanos , Masculino , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II , Antro Pilórico/efectos de los fármacos , Antro Pilórico/enzimología , Antro Pilórico/patología , Ratas , Ratas Wistar , Albúmina Sérica/metabolismoRESUMEN
The plasma arginine vasopressin (AVP), ACTH, and corticosterone levels and the hypothalamic corticotropin-releasing hormone (CRH) content were measured after oral administration of 1 ml of 75% ethanol to rats, a model known to induce acute gastric erosions and stress. Elevated plasma AVP, ACTH, and corticosterone levels were detected 1 h after ethanol administration. Treatment with the vasopressin pressor (V(1)) receptor antagonist [d(CH(2))(5)Tyr(Me)-AVP] before ethanol administration significantly reduced the ACTH and corticosterone level increases. A higher hypothalamic CRH content was measured at 30 or 60 min after ethanol administration. V(1) receptor antagonist injection, 5 min before ethanol administration, inhibited the rise in hypothalamic CRH content. The protein synthesis blocker cycloheximide prevented the hypothalamic CRH content elevation after stress. The AVP-, CRH-, and AVP + CRH-induced in vitro ACTH release in normal anterior pituitary tissue cultures was also prevented by pretreatment with the V(1) receptor antagonist. The results support the hypothesis that stress-induced AVP may not only act directly on the ACTH producing anterior pituitary cells but also indirectly at the hypothalamic level via the synthesis and release of CRH.