Inhibition of vascular nitric oxide-cGMP pathway by plasma from ischemic hindlimb of rats.
The hypothesis was tested that plasma from ischemic hindlimbs facilitates hypertension. Ischemia-induced hypertension was generated in rats by infrarenal aortic cross clamping for 5 h after which plasma was obtained from femoral vein blood. In vitro contractile activity of naive aortic rings incubated for 2 h in plasma collected from ischemic rats demonstrated reduced relaxation to acetylcholine and nitroglycerin. Methylene blue (10(-5) M) induced greater contraction in rings incubated in control vs. ischemic plasma, suggesting that endogenous guanylate cyclase activity is decreased by ischemic plasma. However, 8-bromo-guanosine 3',5'-cyclic monophosphate (cGMP) relaxed equally strips incubated in ischemic or control plasma. Acetylcholine-induced nitrite release was significantly lower in ischemic vs. control plasma-incubated strips (8.6 +/- 2.7 vs. 28.2 +/- 2.3 ng/10 mg tissue wt, respectively). The impaired relaxation to acetylcholine in ischemic plasma-incubated rings was significantly increased by L-arginine but not by prior treatment of ischemic plasma with heating or superoxide dismutase and catalase. These findings suggest the impaired relaxation is mediated through inhibition of the nitric oxide-cGMP pathway. Prolonged blunting of vasodilation by ischemic plasma may therefore contribute to maintenance of a sustained vasoconstriction and ischemic hypertension.
Jin
J S
JS
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA.
Webb
R C
RC
D'Alecy
L G
LG
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001790:Blood Physiological Phenomena; D001808:Blood Vessels / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply; D066298:In Vitro Techniques; D007511:Ischemia / Q000097:blood / Q000378:metabolism*; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D005996:Nitroglycerin; D006152:Cyclic GMP; D000109:Acetylcholine; D008751:Methylene Blue