Potassium channels modulate hypoxic pulmonary vasoconstriction.
The role of Ca2+-activated K+-channel, ATP-sensitive K+-channel, and delayed rectifier K+-channel modulation in the canine pulmonary vascular response to hypoxia was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. Under normoxia, the Ca2+-activated K+-channel blocker tetraethylammonium (1 mM), the ATP-sensitive K+-channel inhibitor glibenclamide (10(-5) M), and the delayed rectifier K+-channel blocker 4-aminopyridine (10(-4) M) elicited a small but significant increase in pulmonary arterial pressure. Hypoxia significantly increased pulmonary arterial and venous resistances and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. Tetraethylammonium, glibenclamide, and 4-aminopyridine potentiated the response to hypoxia on the arterial segments but not on the venous segments and also further decreased pulmonary vascular compliance. In contrast, the ATP-sensitive K+-channel opener cromakalim and the L-type voltage-dependent Ca2+-channel blocker verapamil (10(-5) M) inhibited the vasoconstrictor effect of hypoxia on both the arterial and venous vessels. These results indicate that closure of the Ca2+-activated K+ channels, ATP-sensitive K+ channels, and delayed rectifier K+ channels potentiate the canine pulmonary arterial response under hypoxic conditions and that L-type voltage-dependent Ca2+ channels modulate hypoxic vasoconstriction. Therefore, the possibility exists that K+-channel inhibition is a key event that links hypoxia to pulmonary vasoconstriction by eliciting membrane depolarization and subsequent Ca2+-channel activation, leading to Ca2+ influx.
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Georgia 30912, USA.
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Barman
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008433:Mathematics; D008955:Models, Cardiovascular; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D005905:Glyburide