Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats.
OBJECTIVE
Vasoconstriction of the superior mesenteric artery (SMA) is the earliest hemodynamic event occurring after partial portal vein ligation (PVL). We tested the hypothesis that this early vasoconstriction of the SMA may initiate eNOS up-regulation in PVL.


METHODS
Portal hypertension with or without mesenteric vasoconstriction was induced by differentially calibrated stenosis of the portal vein (PVL-20G and PVL-18G, respectively). In a separate group of rats, mesenteric vasoconstriction was achieved by renal artery ligation. Sham-operated rats were used as controls. Effects of vasoconstriction of the SMA in PVL and RAL rats were evaluated by measuring perfusion pressure changes in isolated SMA beds in response to methoxamine, nitric oxide synthase activity, and eNOS protein expression. Mean arterial pressure, portal pressure, and SMA blood flow were measured by catheterization and Doppler flowmetry. SMA vascular resistance was calculated from arterial pressure, portal pressure, and SMA flow.


RESULTS
There was a significant increase in SMA vascular resistance in PVL-20G (2.33 +/- 0.13 vs. 1.22 +/- 0.03 mm Hg/% flow; P < 0.05) and RAL (2.32 +/- 0.18 vs. 1.18 +/- 0.02 mm Hg/% flow; P < 0.05) but not in PVL-18G, showing mesenteric vasoconstriction in both PVL-20G and RAL groups. The mesenteric vasculature of PVL-20G and RAL animals showed hyporeactivity to methoxamine (P < 0.01). Whereas both PVL groups were portal hypertensive (P < 0.01), RAL rats were not. The SMA hyporeactivity of PVL-20G and RAL rats was corrected by N(G)()-monomethyl-L-arginine, and nitric oxide synthase enzyme activity was significantly higher in PVL-20G and RAL rats (P < 0.05).


CONCLUSIONS
Mesenteric arterial vasoconstriction plays a triggering role in up-regulation of eNOS catalytic activity in the SMA of portal hypertensive rats.
Hepatic Hemodynamic Laboratory, Veterans Administration Medical Center, 950 Campbell Avenue, West Haven, CT 06516, USA.
Ming-Hung
MH
Tsai
Yasuko
Y
Iwakiri
Gregory
G
Cadelina
William C
WC
Sessa
Roberto J
RJ
Groszmann
D000818:Animals; D015153:Blotting, Western; D002384:Catalysis; D006439:Hemodynamics; D006975:Hypertension, Portal / Q000378:metabolism / Q000503:physiopathology*; D008026:Ligation; D008297:Male; D017538:Mesenteric Artery, Superior / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery; D013997:Time Factors; D015854:Up-Regulation; D014661:Vasoconstriction
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat