AJP - Heart and Circulatory Physiology, Vol 272, Issue 2 904-H912, Copyright © 1997 by American Physiological Society

ARTICLES

Inhibition of K(V) and K(Ca) channels antagonizes NO-induced relaxation in pulmonary artery

Y. J. Zhao, J. Wang, L. J. Rubin and X. J. Yuan
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA.

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. Because pulmonary vascular tone is regulated by intracellular free Ca2+ concentration 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 (approximately 0.3 microM) and sodium nitroprusside (SNP, 10 pM) 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 (4-AP, 5-10 mM), which blocks voltage-gated K+ channels (K(V)), and charybdotoxin (200 nM), which blocks Ca2+-activated K+ channels (K(Ca)), both significantly inhibited NO- and SNP-induced PA relaxation. The ATP-sensitive K+ channel blocker glibenclamide, however, had no effect on the relaxation response. The blocking of guanylate cyclase diminished, but did not abolish, the NO-induced relaxation, whereas 4-AP further decreased the NO-induced relaxant response in the presence of the guanylate cyclase inhibitor LY-83583. These data suggest that activation of both K(V) channels and K(Ca) channels by guanosine 3',5'-cyclic monophosphate-dependent and -independent pathways is a mechanism, at least in part, by which NO induces PA relaxation.

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