Enhanced release of nitric oxide in response to changes in flow and shear stress in the superior mesenteric arteries of portal hypertensive rats.
Increased nitric oxide (NO) release has been implicated in the pathogenesis of the hyperdynamic circulation in portal hypertension. NOS 3 (eNOS) causes NO release from the endothelium in response to physical stimuli, such as increased blood flow and shear stress. We evaluated the functional activity of the endothelium in the superior mesenteric arterial bed of portal hypertensive rats through direct measurement of NO metabolites (NOx) during changes in flow and shear stress. The in vitro perfusion system (McGregor) was used in sham and portal vein-ligated (PVL) rats. Shear stress was applied gradually to superior mesenteric arterial beds by increasing the perfusion rate. Flow studies were performed serially before and after incubation with either Krebs solution alone or with the NO-inhibitor, NG-monomethyl-L-arginine (L-NMMA). NOx concentrations in the perfusate were measured using chemiluminescence. The slope of NOx release versus flow-induced shear stress was calculated. Before L-NMMA administration, NOx concentrations and release of NO in PVL rats were significantly elevated in comparison with sham rats at flow rates of 32, 40, and 48 mL/min. The slope of NOx production versus shear stress index was significantly higher in PVL than in sham rats. After L-NMMA incubation, the decrease in slope was significantly larger in PVL rats. This study provides direct evidences of an increased NO synthesis by the superior mesenteric arterial vascular endothelium of PVL animals in response to shear stress. The increased NO output in response to shear stress suggests an adaptative mechanism developed by the vascular endothelial cells in response to a chronic increase in flow-mediated shear stress.
Hori
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Hepatic Hemodynamic Laboratory, Veterans Administration Medical Center, West Haven, CT, USA.
Wiest
R
R
Groszmann
R J
RJ
D000818:Animals; D006975:Hypertension, Portal / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism / Q000503:physiopathology*; D009566:Nitrates / Q000097:blood / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood / Q000378:metabolism; D010477:Perfusion; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D013314:Stress, Mechanical
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide