Enhanced nitric oxide synthase activity in portal hypertensive rabbits.
Portal hypertension (PHT) is characterized by splanchnic hyperemia caused by a reduction in mesenteric vascular resistance. Mediators of this hyperemia include nitric oxide (NO). This is based on several reports indicating a marked splanchnic hyporesponsiveness in PHT to vaso-constrictor stimuli, both in vitro and in vivo, and a subsequent reversal using specific inhibitors of NO synthase (NOS). The objective of this study was to determine directly if the generation of NO is altered in PHT vasculature. Thus, we compared NOS activity in the hyperemic vasculature of normal rabbits and rabbits with PHT (after undergoing partial portal vein ligation). Nicotinamide adenine dinucleotide phosphate diaphorase staining indicated the presence of NOS within the vascular endothelium. Ca(2+)-dependent NOS activity was significantly increased (P < .05) in PHT particulate fractions from the superior mesenteric artery and thoracic aorta, but not from the portal vein. There was no change in NOS activity within the cytosolic fractions. Arterial wall cyclic guanosine monophosphate (cGMP) levels and plasma nitrite levels were both significantly increased in PHT. These results show enhanced NOS activity in PHT hyperemic vessels concurrent with increased tissue cGMP levels. We conclude that enhanced NO synthesis contributes to the hyperdynamic circulation of PHT.
Cahill
P A
PA
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Foster
C
C
Redmond
E M
EM
Gingalewski
C
C
Wu
Y
Y
Sitzmann
J V
JV
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology; D006439:Hemodynamics; D006975:Hypertension, Portal / Q000201:enzymology* / Q000503:physiopathology; D008026:Ligation; D008297:Male; D017538:Mesenteric Artery, Superior / Q000201:enzymology; D009252:NADPH Dehydrogenase / Q000032:analysis; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000097:blood; D011169:Portal Vein / Q000201:enzymology / Q000601:surgery; D011817:Rabbits
D009573:Nitrites; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase; D006152:Cyclic GMP; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester