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Enhanced G‐protein‐induced relaxation in portal hypertensive rats: Role of nitric oxide
Author(s) -
Hou M,
Cahill P A,
Zhang S,
Redmond E M,
Sitzmann J V
Publication year - 1997
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510260104
Subject(s) - nitric oxide , portal hypertension , relaxation (psychology) , medicine , chemistry , pharmacology , cardiology , endocrinology , cirrhosis
Portal hypertension (PHT) is characterized by splanchnic hyperemia due to a reduction in mesenteric vascular resistance. The reasons for the decreased resistance include an increased responsiveness to a vasodilator substance. Because the activation of an inhibitory guanine nucleotide regulatory (Gi) protein can result in endothelium‐dependent relaxation, we tested the hypothesis that exaggerated Gi‐protein induced relaxation via a nitric oxide (NO)‐dependent pathway partly reflects the enhanced Gi‐protein expression in PHT vessels. PHT was created in Sprague‐Dawley rats by a partial portal‐vein ligation. Control animals were sham operated. Using isolated vascular rings in the absence or presence of an intact endothelium, N G ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME), and pertussis toxin, dose response relationships for sodium fluoride (NaF; range, 0.1–4 mmol/L), a Gi protein activator, were determined in a cumulative manner. Gi‐protein expression was determined by Western blotting. NaF caused a dose‐dependent relaxation in both sham and portal hypertensive pre‐contracted vessels, an effect that was significantly inhibited by pertussis toxin, endothelial denudation, and L ‐NAME. Concentrations of NaF greater than 4 mmol/L caused contractions, an effect that was unaffected by L ‐NAME. The NaF‐induced relaxation response was significantly greater in PHT vessels as compared with sham concomitant with increased Gi‐protein expression in PHT vessels. These data suggest that the enhanced endothelial Gi‐protein‐induced relaxation in PHT vessels may partly reflect enhanced expression of Gi‐proteins in PHT vessels and may, thus, represent an important mechanism for exaggerated NO‐dependent relaxation in the PHT vasculature.