Nitric oxide production in arterial vessels of cirrhotic rats.
Indirect evidence exists implicating vascular nitric oxide in the pathogenesis of arterial vasodilation in cirrhosis. In the current study, a coincubation assay to estimate the vascular nitric oxide production was developed and the nitric oxide production by arterial segments of cirrhotic and control rats was assessed. In the assay, measurement of reporter monolayer cell-associated cGMP levels allows the influence of nitric oxide released by arterial segments to be determined. RFL-6 cells served as reporter cells. Nitric oxide production was determined in thoracic aorta and mesenteric arteries of 22 control rats, 10 cirrhotic rats without ascites, and 12 cirrhotic rats with ascites. Basal and bradykinin-stimulated (10(-6) mol/L) intracellular content of nitric oxide-dependent cGMP was significantly higher in RFL-6 cells coincubated with aortic segments of cirrhotic rats with (21.3 +/- 3.6 pmol/10(5) cells, P < .05 and 44.7 +/- 7.0 pmol/10(5) cells, P < .025) and without ascites (15.3 +/- 3.0 pmol/10(5) cells, P < .05 and 43.2 +/- 7.6 pmol/10(5) cells, P < .05) than in those incubated with aortic segments of control rats (9.7 +/- 1.3 and 19.5 +/- 2.5 pmol/10(5) cells). RFL-6 cells exposed to bradykinin-stimulated mesenteric arterial segments of cirrhotic rats also showed increased cGMP content (ascitic: 2.73 +/- 0.31 pmol/10(5) cells, P < .005; nonascitic: 2.58 +/- 0.51 pmol/10(5) cells, P < .025) compared with cells exposed to control mesenteric arterial segments (1.28 +/- 0.15 pmol/10(5) cells). No differences between cirrhotic and control vessels were observed after endothelium denudation.(ABSTRACT TRUNCATED AT 250 WORDS)
Ros
J
J
Hormonal Laboratory, Hospital Clinic i Provincial, University of Barcelona, Spain.
Jiménez
W
W
Lamas
S
S
Clària
J
J
Arroyo
V
V
Rivera
F
F
Rodés
J
J
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D001671:Biochemistry / Q000379:methods; D001920:Bradykinin / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide; D006152:Cyclic GMP; D001920:Bradykinin