Potassium channels modulate canine pulmonary vasoreactivity to protein kinase C activation

The role of Ca2+-activated K(-+)channel, ATP-sensitive K+-channel, and dela yed rectifier K(-+)channel modulation in the canine pulmonary vascular resp onse to protein kinase C (PKC) activation was determined in the isolated bl ood-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) sign ificantly increased pulmonary arterial and pulmonary venous resistances and pulmonary capillary pressure and decreased total vascular compliance by de creasing both microvascular and large-vessel compliances. The Ca2+-activate d K+-channel blocker tetraethylammonium ions (1 mM), the ATP-sensitive K+-c hannel inhibitor glibenclamide (10(-5) M), and the delayed rectifier K+-cha nnel blocker 4-aminopyridine(10(-4) M) potentiated the presser response to both PMA and THX on the arterial and venous segments and also further decre ased pulmonary vascular compliance. In contrast, the ATP-. sensitive K+-cha nnel 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 presser 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, in dicating that K+ channels modulate the canine pulmonary vasoconstrictor res ponse to PKC activation.