Mechanisms of hypoxic vasodilation in ferret pulmonary arteries
Wiener, C.M.; Banta, M.R.; Dowless, M.S.; Flavahan, N.A.; Sylvester, J.T.
American Journal of Physiology 269(3 Pt 1): L351-L357
1995
ISSN/ISBN: 0002-9513 PMID: 7573469 Document Number: 451156
To investigate the mechanism of hypoxic pulmonary vasodilation we measured isometric tension in rings from ferret third- to fifth-generation intrapulmonary arteries mounted in organ baths (37 degree C, 28% O-2-5% CO-2). 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 (K-ATP) 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-2+-activated K+ (K-Ca) channels with charybdotoxin potentiated the vasoconstrictor response to PE but had no effect on hypoxic vasodilation. The nonspecific K+-channel inhibitor tetraethylammonium (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 K-ATP-channel independent vasodilation. These results suggest that in isolated ferret pulmonary arteries hypoxia causes vasodilation partially by activating smooth muscle K-ATP channels. Activation of a TEA-sensitive channel that is not a K-ATP or K-Ca channel may also contribute to hypoxic vasodilation.