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

INSERM U14, Plateau de Brabois, C.O. 10, Vanduvre-les-Nancy and Service des Maladies Respiratoires et Réanimation Respiratoire, CHU Nancy-Brabois, Vanduvre-les-Nancy, France

CORRESPONDENCE: F. Chabot, Service des Maladies Respiratoires et Réanimation Respiratoire, CHU Nancy-Brabois, rue du Morvan, 54500, Vanduvre-les-Nancy, France. Fax: 33 0383154023

Because hypoxic pulmonary vasoconstriction occurs mainly in the small pulmonary arteries, the authors investigated the effects of drugs acting on the nitric oxide (NO) pathway and the calcium and potassium channels in the peripheral pulmonary circulation, without interference with the overall pulmonary or systemic circulation.

Mixed venous blood was infused in wedged areas to study the pressure/flow relationship and to compute peripheral pulmonary vascular resistance (PPVR). The authors studied the effects of N-nitro-l-arginine methyl ester (l-NAME), an NO synthase inhibitor, sodium nitroprusside (SNP, an NO donor), the calcium channel blockers verapamil, nifedipine and nicardipine, and the potassium channel opener levcromakalim, during normoxia and acute mild normocapnic 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 increase by l-NAME, SNP decreased PPVR during normoxia (–24%; p<0.05) and hypoxia (–23%; p<0.05). Verapamil, nifedipine and nicardipine did not modify PPVR during normoxia but during hypoxia they decreased PPVR (–28%, nonsignificant; –27%, p<0.01 and –33%, p<0.05, respectively). Levcromakalim did not modify PPVR during normoxia or hypoxia.

In conclusion, the nitric oxide pathway and voltage-dependent calcium channels, and not adenosine triphosphate sensitive potassium channels, play an important role in the control of peripheral pulmonary circulation in dogs.

Keywords: anaesthetized dogs, ATP-sensitive potassium channel opener, calcium channel inhibitors, hypoxia, peripheral pulmonary circulation, pulmonary vasoreactivity