title: NO overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats.
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 alpha-adrenoreceptor agonist methoxamine (30 and 100 microM) before and after incubation with the NO inhibitor, Nomega-nitro-L-arginine (L-NNA, 10(-4) M). Perfusate NO metabolite (NOx) 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 NOx production vs. flow-induced shear stress, higher increases in perfusate NOx 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.
authors: Hepatic Hemodynamic Laboratory, Veterans Affairs Medical Center, West Haven 06516, Connecticut, USA.
authors: R
authors: R
authors: Wiest
authors: V
authors: V
authors: Shah
authors: W C
authors: WC
authors: Sessa
authors: R J
authors: RJ
authors: Groszmann
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D006975:Hypertension, Portal / Q000201:enzymology* / Q000503:physiopathology*; D007700:Kinetics; D008163:Luminescent Measurements; D008297:Male; D017538:Mesenteric Artery, Superior / Q000503:physiopathology*; D008729:Methoxamine / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000502:physiology*; D013314:Stress, Mechanical
chemical_list: D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D008729:Methoxamine