Role of NO pathway, calcium and potassium channels in the peripheral pulmonary vascular tone in dogs

Because hypoxic pulmonary vasoconstriction occurs mainly in the small pulmo nary arteries, the authors investigated the effects of drugs acting on the nitric oxide (NO) pathway and the calcium and potassium channels in the per ipheral pulmonary circulation, without interference with the overall pulmon ary or systemic circulation. Mixed venous blood was infused in wedged areas to study the pressure/flow r elationship and to compute peripheral pulmonary vascular resistance (PPVR). The authors studied the effects of NO-nitro-L-arginine methyl ester (L-NAM E), an NO synthase inhibitor, sodium nitroprusside (SNP, an NO donor), the calcium channel blockers verapamil, nifedipine and nicardipine, and the pot assium channel opener leveromakalim, during normoxia and acute mild normoca pnic hypoxia. In the peripheral pulmonary circulation, L-NAME caused an increase in PPVR during normoxia (+95%; p<0.001) and hypoxia (+60%; p<0.01). Following the i ncrease by L-NAME, SNP decreased PPVR during normoxia (-24%; p<0.05) and hy poxia (-23%; p<0.05). Verapamil, nifedipine and nicardipine did not modify PPVR during normoxia but during hypoxia they decreased PPVR (-28%, nonsigni ficant; -27%, p<0.01 and -33%, p<0.05, respectively). Leveromakalim did not modify PPVR during normoxia or hypoxia. In conclusion, the nitric oxide pathway and voltage-dependent calcium chann els, and not adenosine triphosphate sensitive potassium channels, play an i mportant role in the control of peripheral pulmonary circulation in dogs.