title: Potassium channels modulate canine pulmonary vasoreactivity to protein kinase C activation.
abstract: The role of Ca2+-activated K+-channel, ATP-sensitive K+-channel, and delayed rectifier K+-channel modulation in the canine pulmonary vascular response to protein kinase C (PKC) activation was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. The PKC activators phorbol 12-myristate 13-acetate (PMA; 10(-7) M) and thymeleatoxin (THX; 10(-7) M) significantly increased pulmonary arterial and pulmonary venous resistances and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. The Ca2+-activated K+-channel blocker tetraethylammonium ions (1 mM), the ATP-sensitive K+-channel inhibitor glibenclamide (10(-5) M), and the delayed rectifier K+-channel blocker 4-aminopyridine (10(-4) M) potentiated the pressor response to both PMA and THX on the arterial and venous segments and also further decreased pulmonary vascular compliance. In contrast, the ATP-sensitive K+-channel opener cromakalim (10(-5) M) attenuated the vasoconstrictor effect of PMA and THX on both the arterial and venous vessels. In addition, membrane depolarization by 30 mM KCl elicited an increase in the pressor response to PMA. These results indicate that pharmacological activation of PKC elicits pulmonary vasoconstriction. Closure of the Ca2+-activated K+ channels, ATP-sensitive K+ channels, and delayed rectifier K+ channels as well as direct membrane depolarization by KCl potentiated the response to PMA and THX, indicating that K+ channels modulate the canine pulmonary vasoconstrictor response to PKC activation.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Georgia 30912, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Barman
mesh_terms: D000818:Animals; D003187:Compliance / Q000187:drug effects; D004285:Dogs; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D008297:Male; D010703:Phorbol Esters / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
chemical_list: D010703:Phorbol Esters; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C080287:thymeleatoxin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate