Pulmonary vasoreactivity to endothelin-1 at elevated vascular tone
is modulated by potassium channels .
Barman, Scott A.
Department of Pharmacology, and Toxicology, Medical College of
Georgia, Augusta, Georgia 30912
APStracts 2:0359A, 1995.
The role of potassium (K+) channels on the pressor effect of
endothelin-1 (ET-1) on vascular resistance and compliance in the
canine pulmonary circulation was studied using three different K+
channel inhibitors in isolated blood perfused dog lungs when vascular
tone was elevated with U-46619: 1) 10-6 M glibenclamide, a potent and
selective blocker of ATP-sensitive K+ channels, 2) 1mM
tetraethylammonium ions (TEA), an inhibitor of Ca2+-dependent K+
channels, and 3) 10-4 M 4-aminopyridine, a non-specific inhibitor of
K+ channels. The results of the present study showed that under
control vascular tone, 10-8 M ET-1 increased total vascular
resistance and capillary pressure by increasing postcapillary
resistance. In addition, ET-1 decreased total vascular compliance.
When vascular tone was elevated, ET-1 elicited an initial transient
vasodilation followed by a sustained mild vasoconstriction that was
lesser in magnitude than that observed under normal vascular tone. In
addition, the increase in postcapillary resistance, capillary
pressure, and decrease in vascular compliance that was observed with
ET-1 at normal vascular tone was not present. Pretreatment with
glibenclamide, TEA, and 4-aminopyridine at elevated vascular tone
significantly potentiated the pressor effect of ET-1 and TEA blocked
the transient vasodilation to ET-1. These data indicate that when
pulmonary vasomotor tone is elevated with U-46619, Ca2+-dependent K+
channels may play a significant role in mediating the vasodilator
response to ET-1, while ATP-sensitive, Ca2+-dependent, and other
voltage activated K+ channels attenuate the pulmonary vasoconstrictor
response to ET-1.
Received 14 February 1995; accepted in final form 7 August 1995.
APS Manuscript Number A180-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.