SEGMENTAL VASCULAR-RESPONSES TO VOLTAGE-GATED CALCIUM-CHANNEL POTENTIATION IN RAT LUNG

We determined lung vascular responses to voltage-gated Ca2+ channel potentiation with BAY K 8644 (BAY). We anesthetized 46 rats (Sprague-Dawley; halothane and pentobarbital) and then excised and perfused their lungs at constant blood flow of 25 +/- 2 (SE) ml . kg-1 . min-1 at constant airway and left atrial pressures of 5 and 6 cmH2O, respectively. Pulmonary arterial pressure (Ppa) increased from 13.3 +/- 0.3 cmH2O at baseline to 17.3 +/- 1.3 cmH2O after BAY (2.8 x 10(-6) M; n = 5; P < 0.01). As determined by micropuncture, arteriolar and venular (Pven) pressures did not change. Increase of perfusate Ca2+ (16 x 10(-3) M; n = 8) similarly increased Ppa. N(G)-monomethyl-L-arginine ( 2 X 10(-4) M), an inhibitor of endothelium-derived relaxing factor, augmented the pressor effect of BAY when given after (n = 4) but not before (n = 4) BAY (P < 0.01). Prior cyclooxygenase blockade with indomethacin (5 mg/kg; n = 5) attenuated the Ppa response to BAY (P < 0.01). None of these agents changed Pven. To confirm vasoactivity in veins, we induced smooth muscle depolarization with KCl (20 X 10(-3) M; n = 6) and receptor-mediated responses with histamine (3 x 10(-4) M; n = 7). Both of these agents increased Pven markedly (P < 0.01). We interpret that, in rat lung, BAY causes arterial but not venous constriction, because the venous segment differs from the arterial with regard to Ca2+ channel potentiation.