No overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats

Reiner Wiest, Vijay Shah, William C. Sessa, Roberto J. Groszmann

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

Chronic high blood flow and the hyperdynamic circulatory syndrome in portal hypertension are associated with endothelial constitutive nitric oxide (NO) synthase (eNOS) upregulation and increased NO release. In portal vein- ligated (PVL) rats the splanchnic circulation is not yet hyperdynamic on day 3 postoperatively. In vitro perfused superior mesenteric arteries (SMAs) of day 3 PVL and sham rats were challenged with increasing flow rates or the α- adrenoreceptor agonist methoxamine (30 and 100 μM) before and after incubation with the NO inhibitor, N(ω)-nitro-L-arginine (L-NNA, 10-4 M). Perfusate NO metabolite (NO(x)) concentrations were measured by chemiluminescence. PVL rats expressed a significant hyporesponsiveness to increases in flow rate or methoxamine that was overcome by incubation with L- NNA. The PVL vasculature showed significantly higher slopes of NO(x) production vs. flow-induced shear stress, higher increases in perfusate NO(x) concentration in response to methoxamine, and higher eNOS protein levels (Western blot) compared with sham rats. In conclusion, eNOS-upregulation and increased NO release by the SMA endothelium occur before the development of the hyperdynamic splanchnic circulation, suggesting a primary role of NO in the pathogenesis of arterial vasodilatation.

Original languageEnglish (US)
Pages (from-to)G1043-G1051
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume276
Issue number4 39-4
StatePublished - Apr 1 1999

Keywords

  • Endothelial nitric oxide synthase
  • Superior mesenteric artery
  • Vasodilation

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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