Inhibition of voltage-gated and ca2+-activated k+ channels
antagonizes nitric oxide induced relaxation in pulmonary artery.
Zhao, Yi-Ju, Jian Wang, Lewis J. Rubin, and Xiao-Jian Yuan.
Department of Medicine, Division of Pulmonary and Critical Care
Medicine; Department of Physiology, University of Maryland School of
Medicine, Baltimore, Maryland 21201
APStracts 3:0423H, 1996.
Endogenous nitric oxide (NO) may contribute to the maintenance of
normal pulmonary vasomotor tone and inhaled NO is used to treat
patients with pulmonary hypertension. Since pulmonary vascular tone
is regulated by [Ca2+]i and membrane potential which are controlled
by the K+ channel activity in pulmonary artery (PA) smooth muscle
cells, we sought to determine whether K+ channels are involved in NO
-induced relaxation and if so, which types of K+ channels are
responsible. Authentic NO (0.3 [mu]M) and sodium nitroprusside (SNP,
10 [mu]M) both produced significant relaxation in isolated PA rings
precontracted by increasing extracellular K+ concentration. Further
elevation of the K+ concentration from 20 to 60 mM resulted in a
significant increase in contraction, but caused a marked decline in
SNP- and NO-mediated PA relaxation. The dependence of SNP- and NO
-induced relaxation on transmembrane K+ gradient suggests that K+
efflux through K+ channels is involved in these effects. Furthermore,
4-aminopyridine (5-10 mM), which blocks voltage-gated K+ channels,
and charybdotoxin (200 nM), which blocks Ca2+-activated K+ channels,
both significantly inhibited NO- and SNP-induced PA relaxation. The
ATP-sensitive K+ channel blocker, glibenclamide, however, had no
effect on the relaxation response. Block of guanylate cyclase
diminished, but did not abolish, the NO-induced relaxation, whereas
4-aminopyridine further decreased the NO-induced relaxant response in
the presence of the guanylate cyclase inhibitor, LY-83583. These data
suggest that activation of both voltage-gated K+ channels and Ca2+
-activated K+ channels by cGMP-dependent and -independent pathways is
a mechanism, at least in part, by which NO induces PA relaxation.
Received 4 June 1996; accepted in final form 9 September 1996.
APS Manuscript Number H501-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996