Dissociation between pressor sensitivity in vivo and contractile reactivity in vitro to angiotensin II in rats with experimental cirrhosis.
1. Decreased pressor sensitivity to angiotensin II occurs in cirrhosis, but the mechanism remains unclear. 2. Angiotensin II dose-response studies were performed in conscious, chronically instrumented cirrhotic and control rats, and angiotensin II concentration-response studies were performed in isolated blood vessels obtained from similar groups of animals. 3. Cirrhotic rats demonstrated a significantly decreased pressor response to angiotensin II (5-80 ng/kg intravenously). However, angiotensin II-generated tension in thoracic aortic rings isolated from cirrhotic rats and studied in vitro was not impaired. These findings are consistent with the concept that circulating vasodilator substances in cirrhosis rather than an abnormality intrinsic to vascular smooth muscle cells are responsible for the decreased pressor sensitivity to angiotensin II in vivo. 4. Pretreatment with the cyclo-oxygenase inhibitor indomethacin (3 mg/kg intravenously) restored pressor sensitivity to angiotensin II to normal, suggesting that cyclo-oxygenase products, possibly vasodilator prostaglandins, may be involved in mediating pressor resistance to this hormone in vivo.
Leehey
D J
DJ
Department of Medicine, Veterans Affairs Hospital, Hines, Illinois 60141.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000804:Angiotensin II; D007213:Indomethacin