MECHANISMS OF HYPOXIC VASODILATION IN FERRET PULMONARY-ARTERIES

To investigate the mechanism of hypoxic pulmonary vasodilation we meas ured isometric tension in rings from ferret third- to fifth-generation intrapulmonary arteries mounted in organ baths (37 degrees C, 28% O-2 -5% CO2). After precontraction with phenylephrine (PE), hypoxia caused a brief transient vasoconstriction followed by marked vasodilation. E ndothelial denudation did not affect the steady-state response. In ves sels without endothelium, inhibition of cyclooxygenase and nitric oxid e synthase had no effect on the response to hypoxia. Inhibition of ATP -dependent K+ channels (K-ATP) with glibenclamide, linogliride, or tol butamide had no effect on normoxic tone before PE or the vasoconstrict or response to PE but inhibited hypoxic vasodilation. Inhibition of Ca 2+-activated K+ (K-Ca) channels with charybdotoxin potentiated the vas oconstrictor response to PE but had no effect on hypoxic vasodilation. The nonspecific K+-channel inhibitor tetraethylammonium (TEA) potenti ated the response to PE and inhibited hypoxic vasodilation. Glibenclam ide plus TEA inhibited hypoxic vasodilation more than either agent alo ne, suggesting that TEA inhibited the K-ATP-channel independent vasodi lation. These results suggest that in isolated ferret pulmonary arteri es hypoxia causes vasodilation partially by activating smooth muscle K -ATP channels. Activation of a TEA-sensitive channel that is not a K-A TP Or K-Ca channel may also contribute to hypoxic vasodilation.