TY - JOUR
T1 - No overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats
AU - Wiest, Reiner
AU - Shah, Vijay
AU - Sessa, William C.
AU - Groszmann, Roberto J.
PY - 1999/4
Y1 - 1999/4
N2 - 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.
AB - 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.
KW - Endothelial nitric oxide synthase
KW - Superior mesenteric artery
KW - Vasodilation
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U2 - 10.1152/ajpgi.1999.276.4.g1043
DO - 10.1152/ajpgi.1999.276.4.g1043
M3 - Article
C2 - 10198349
AN - SCOPUS:0032938259
SN - 0193-1857
VL - 276
SP - G1043-G1051
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 4 39-4
ER -