Inhibition of the vascular nitric oxide-cgmp pathway by plasma from the ischemic hindlimb of rats. Jin, Jong-Shiaw, R. Clinton Webb, and Louis G. D'alecy. Department of Physiology, The University of Michigan Medical School, Ann Arbor, MI 48109-0622 (U.S.A.)
APStracts 2:0040H, 1995.
The hypothesis was tested that plasma from ischemic hind limbs facilitates hypertension. Ischemia-induced hypertension was generated in rats by infrarenal aortic cross-clamping for 5 hours after which plasma was obtained from femoral vein blood. In vitro contractile activity of naive aortic rings incubated for 2 hours in plasma collected from ischemic rats demonstrated reduced relaxation to acetylcholine and nitroglycerin. Methylene blue (10-5M) induced greater contraction in rings incubated in control verses ischemic plasma suggesting that endogenous guanylate cyclase activity is decreased by ischemic plasma. However, 8-bromo-cyclic GMP relaxed equally strips incubated in ischemic or control plasma. Acetylcholine induced nitrite release was significantly lower in ischemic verses control plasma incubated strips (8.6 +/- 2.7 vs. 28.2 +/- 2.3 ng/10mg tissue weight, respectively). The impaired relaxation to acetylcholine in ischemic plasma incubated rings was significantly increased by L-arginine, but not by prior treating ischemic plasma with heating or superoxide dismutase and catalase. These findings suggest the impaired relaxation is mediated through inhibition of the nitric oxide-cyclic GMP pathway. Prolonged blunting of vasodilation by ischemic plasma may therefore contribute to maintenance of a sustained vasoconstriction and ischemic hypertension. 

Received 25 November 1994; accepted in final form 6 February
1995.
APS Manuscript Number H946-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.