Journal of Applied Physiology, Vol 78, Issue 6 2062-2069, Copyright © 1995 by American Physiological Society
Role of G proteins in the vasodilator response to endothelin isopeptides in vivo
H. L. Lippton, Q. Hao, O. Erdemli and A. Hyman
Department of Surgery, Tulane Medical School, Louisiana State University Medical School, New Orleans 70112, USA.
The purpose of the present study was to determine the influence of
pertussis toxin (PTX) on the pulmonary and systemic vasodilator responses
to endothelin (ET) isopeptides in the intact cat under conditions of
constant pulmonary blood flow and left atrial pressure. When pulmonary
vasomotor tone was actively increased by an intralobar arterial infusion of
U-46619, intralobar arterial bolus injections of ET-1, ET-2, and ET-3
decreased lobar arterial pressure and systemic vascular resistance in a
dose-related manner. The vasodilator responses to ET-1 and ET-2 in the cat
lung were abolished by PTX pretreatment, whereas PTX pretreatment did not
alter the pulmonary vasodilator response to ET-3 and cromakalim, a specific
ATP-sensitive potassium (KATP) channel activator, and the systemic
vasodilator responses to all ET isopeptides studied. Glipizide, an
inhibitor of KATP channels, inhibited the pulmonary vasodilator responses
to ET-1, ET-2, and ET-3, whereas the systemic vasodilator responses to
these isopeptides were not changed. The present data are the first to
provide a functional correlate in vivo suggesting the existence of
different signal transduction mechanisms for two pulmonary vascular ET
receptor subtypes, ETA-like that is PTX sensitive and has greater
sensitivity to ET-1 and ET-2 (than to ET-3) and ETc-like that is PTX
insensitive and has sensitivity to ET-3 (than to ET-1 and ET-2). However,
both ET-receptor subtypes promote vasodilation in the adult pulmonary
vascular bed by activating KATP channels.(ABSTRACT TRUNCATED AT 250 WORDS)
