AJP - Heart and Circulatory Physiology, Vol 270, Issue 4 1484-H1492, Copyright © 1996 by American Physiological Society

ARTICLES

Calcium channel activity increased by plasma from ischemic hindlimbs of rats: role of an endogenous NO synthase inhibitor

J. S. Jin, D. W. Wilde, R. C. Webb and L. G. D'Alecy
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA.

We tested the hypothesis that an endogenous nitric oxide synthase (NOS) inhibitor released from ischemic hindlimbs increases the activity of calcium channels in vascular smooth muscle, thus contributing to the increased contractile response to calcium agonists. Hindlimb ischemia was generated in rats by infrarenal aortic cross clamping for 5 h, after which plasma was obtained from femoral vein blood. Incubating naive aortic rings (endothelium intact) for 2 h in plasma collected from ischemic rats significantly reduced relaxation to acetylcholine in precontracted rings and increased contraction to the calcium channel agonist, BAY K 8644. However, in isolated smooth muscle cells (without endothelium) loaded with fura-2, no difference was noted in BAY K 8644-stimulated intracellular calcium concentration. The contractile responses to sodium fluoride, serotonin, and calcium ionophore A23187 were not different in either ischemic or control plasma-incubated rings. The augmentation of the contractile response to BAY K 8644 was significantly inhibited by nitroglycerin (10-8 M) and by exposure to calcium-free solution. N omega-nitro-L-arginine (without plasma incubation)-pretreated rings also demonstrated hyperresponsiveness to BAY K 8644. The increase in responsiveness to BAY K 8644 exhibited a negative correlation with the maximal relaxation to acetylcholine (r = -0.99), suggesting that the apparent increase in activity of calcium channels is mediated through inhibition of nitric oxide by an endogenous NOS inhibitor on endothelium.

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