Mechanisms of hypoxic vasodilation in ferret pulmonary arteries. Wiener, Charles M., Marilyn R. Banta, Michelle S. Dowless, Nicholas A. Flavahan, and J. T Sylvester. Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205
APStracts 2:0074L, 1995.
To investigate the mechanism of hypoxic pulmonary vasodilation we measured isometric tension in rings from ferret 3rd-5th generation intrapulmonary arteries mounted in organ baths (37o C, 28% O2/5% CO2). After precontraction with phenylephrine (PE), hypoxia caused a brief transient vasoconstriction followed by marked vasodilation. Endothelial denudation did not affect the steady state response. In vessels without endothelium, inhibition of cyclooxygenase and nitric oxide synthase had no effect on the response to hypoxia. Inhibition of ATP-dependent K+ channels (KATP) with glibenclamide, linogliride, or tolbutamide had no effect on normoxic tone before PE or the vasoconstrictor response to PE, but inhibited hypoxic vasodilation. Inhibition of Ca++-activated K+ (KCa) channels with charybdotoxin potentiated the vasoconstrictor response to PE, but had no effect on hypoxic vasodilation. The non-specific K+ channel inhibitor, TEA, potentiated the response to PE and inhibited hypoxic vasodilation. Glibenclamide plus TEA inhibited hypoxic vasodilation more than either agent alone, suggesting that TEA inhibited the KATP channel independent vasodilation. These results suggest that in isolated ferret pulmonary arteries hypoxia causes vasodilation partially by activating smooth muscle KATP channels. Activation of a TEA-sensitive channel that is not a KATP or KCa channel may also contribute to hypoxic vasodilation. 

Received 17 October 1994; accepted in final form 28 April 1995.
APS Manuscript Number L296-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  9 May 1995.