Mechanisms of hypoxic vasodilation in ferret pulmonary arteries.
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.
Wiener
C M
CM
Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Banta
M R
MR
Dowless
M S
MS
Flavahan
N A
NA
Sylvester
J T
JT
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005289:Ferrets; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery / Q000503:physiopathology*; D011758:Pyrroles / Q000494:pharmacology; D014664:Vasodilation; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology
D001578:Benzopyrans; D016861:Cyclooxygenase Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D019001:Nitric Oxide Synthase