Nitroglycerin relaxes rat tail artery primarily by decreasing [
ca2-]i sensitivity and partially by repolarization and inhibiting
ca2- release.
Chen, Xiao-Liang, and Christopher M. Rembold.
Cardiovascular Division, Departments of Internal Medicine and
Physiology, University of Virginia Health Sciences Center,
Charlottesville, Virginia 22908 USA
APStracts 3:0070H, 1996.
There are at least five mechanisms hypothesized to account for cyclic
guanosine monophosphate (cGMP) induced relaxation of arterial smooth
muscle: 1) repolarization, 2) inhibition of Ca2- release, 3)
inactivation of L type Ca2- channels, 4) enhancement of Ca2-
efflux/sequestration, and 5) decreasing the [Ca2-]i sensitivity of
force. The goal of this study was to investigate the physiologic
relevance of these five mechanisms in the intact rat tail artery. We
stimulated deendothelialized rat tail artery with phenylephrine or
high [K-]o and then relaxed the tissue by adding nitroglycerin to
increase [cGMP]. We measured membrane potential (Em) with
microelectrodes, [Ca2-]i with Fura 2, and isometric force with a
strain gauge transducer. We found that decreases in the [Ca2-]i
sensitivity of force accounted for most of the nitroglycerin induced
relaxation of tissues prestimulated with maximal (1 [mu]M)
phenylephrine or 30 mM [K-]o. In submaximally (0.1 - 0.3 [mu]M)
phenylephrine prestimulated tissues, the nitroglycerin induced
relaxation was caused primarily by a decrease in the [Ca2-]i
sensitivity of force and partially by repolarization and the
resultant decrease in [Ca2-]i. Nitroglycerin also partially
attenuated transient increases in [Ca2-]i and force induced by 100
[mu]M phenylephrine in the absence of extracellular Ca2-, indicating
that nitroglycerin also inhibited intracellular Ca2- release.
Nitroglycerin induced relaxation was not associated with inactivation
of Ca2- channels or enhancement of Ca2- efflux/sequestration. These
data suggest that nitroglycerin primarily relaxes precontracted rat
tail artery primarily by decreasing the [Ca2-]i sensitivity of force.
Received 21 July 1995; accepted in final form 17 January 1996.
APS Manuscript Number H689-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 14 February 96