AJP - Cell Physiology, Vol 258, Issue 6 C1025-C1030, Copyright © 1990 by American Physiological Society
Nickel inhibits endothelin-induced contractions of vascular smooth muscle
K. Blackburn and R. F. Highsmith
Department of Physiology and Biophysics, University of Cincinnati College of Medicine, Ohio 45267.
Endothelin (ET)-induced contractions of vascular smooth muscle (VSM) are
dependent on extracellular Ca2+ yet display only partial sensitivity to
L-type Ca2+ antagonists. The purpose of this study was to evaluate the
effect of nickel (Ni2+), a Ca2+ channel antagonist with clearly documented
differential potency toward L- vs. T-type Ca2+ currents on ET-mediated
contractions in VSM. Treatment of rings of left anterior descending porcine
coronary artery (LAD) with Ni2+ produced a profound dose-dependent
inhibition of isometric force development in response to porcine ET (ET-1).
At a concentration of 360 microM, Ni2+ exerted a significant inhibitory
effect on contracture in response to doses of ET-1 ranging from 3 to 100
nM. In contrast, the same concentration of Ni2+ failed to significantly
affect peak force development in response to KCl depolarization (5-77 mM)
or to phenylephrine (0.3-30 mM). In addition, 360 microM Ni2+ significantly
inhibited the contractile response of rat aorta to 10 nM ET-1. We conclude
that ET-1 activates a Ni2(+)-sensitive process in VSM which may signal an
additional Ca2+ influx pathway that appears to be functionally distinct
from the L-type Ca2+ channel.
