Vascular nitric oxide production during the development of two experimental models of portal hypertension.
OBJECTIVE
The aim of this study was to determine the relative roles of constitutive NOS (NOS3) and inducible NOS (NOS2) isoforms during the development of two models of portal hypertension in rats.


METHODS
Vascular reactivity of aortic rings for norepinephrine was performed in control, sham-operated, portal-vein-stenosed and secondary biliary cirrhotic rats 1, 4, 7, 14 and 28 days after surgery. NOS activity and nitrate plasma levels were also measured.


RESULTS
An impaired response to norepinephrine observed in sham-operated, portal-vein-stenosed and cirrhotic rats at days 1 and 4 compared with controls was reversed after L-NNA and aminoguanidine. Portal hypertensive rats remained hyporeactive at days 7, 14 and 28 compared with sham-operated rats. At days 7 and 14 in portal-vein-stenosed rats, vascular hyporeactivity was reversed by L-NNA and W7. At days 14 and 28 in cirrhotic rats, vascular hyporeactivity was reversed by L-NNA and W7. Nitrate levels increased at day 1 in the 3 groups, and increased at days 14 and 28 in portal hypertensive rats. Total NOS-activity increased in cirrhotic rats at day 28, in portal-vein-stenosed rats at day 14, and in sham-operated rats at day 1 compared to controls. NOS2 activity increased only in sham-operated rats at day 1.


CONCLUSIONS
This study shows that for two models of portal hypertension, increased NO production in the first days is related to NOS2 induction secondary to surgery. On the other hand, when portal hypertension has fully developed, the NOS3 isoform appears to play the major role.
Gadano
A C
AC
Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM, Hôpital Beaujon, Clichy, France.
Sogni
P
P
Heller
J
J
Moreau
R
R
Bories
P N
PN
Lebrec
D
D
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D006146:Guanidines / Q000494:pharmacology; D006975:Hypertension, Portal / Q000201:enzymology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008105:Liver Cirrhosis, Biliary / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009638:Norepinephrine / Q000494:pharmacology; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D013927:Thrombosis / Q000201:enzymology / Q000503:physiopathology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D006146:Guanidines; D009566:Nitrates; D013449:Sulfonamides; D019323:omega-N-Methylarginine; C017967:W 7; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; C004479:pimagedine; D009638:Norepinephrine