K+ Channel Activation with Minoxidil Stimulates Nasal-Epithelial Ion Transport and Blunts Exaggerated Hypoxic Pulmonary Hypertension

Abstract

Increased pulmonary capillary pressure and inhibition of alveolar Na+ transport putatively contribute to the formation of pulmonary edema in alveolar hypoxia such as at high altitude. Since both events might be linked to the inhibition of K+ channels, we studied whether in vivo application of minoxidil, a stimulator of ATP-gated K channels (K+ ATP channel activator) prevents both effects. In a double- blind, placebo-controlled crossover study on 17 volunteers with no known susceptibility to high altitude pulmonary edema, we tested whether a single dose of minoxidil (5 mg) prevents pulmonary hypertension and inhibition of nasal-epithelial Na+ transport in normobaric hypoxia (12% O2, 2 h). In hypoxia, arterial SO2 was decreased to about 80%, and systolic pulmonary artery pressure (PAP) measured by Doppler echocardiography increased significantly from approximately 25 mmHg (normoxia) to approximately 38 mmHg (hypoxia; range 22 to 61 mmHg). Minoxidil decreased PAP in hypoxia in those individuals who had the highest increase in PAP in hypoxia when taking placebo. Nasal potentials decreased by about 10% in hypoxia. Although minoxidil had no effect on nasal potentials in normoxia, it increased nasal potentials significantly above normoxic control values after 2-h hypoxia. These results show that the K+ ATP activator minoxidil prevents the decrease in nasal-epithelial potential by hypoxia and seems to blunt an exaggerated increase in PAP in acute hypoxia.