Wiener C M, Banta M R, Dowless M S, Flavahan N A, Sylvester J T
Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Am J Physiol. 1995 Sep;269(3 Pt 1):L351-7. doi: 10.1152/ajplung.1995.269.3.L351.
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 degrees 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(2+)-activated K+ (KCa) channels with charybdotoxin potentiated the vasoconstrictor response to PE but had no effect on hypoxic vasodilation. The nonspecific K(+)-channel inhibitor tetraethyl-ammonium (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.
