ENDOTHELIN-1 IN PULMONARY-HYPERTENSION ASSOCIATED WITH HIGH-ALTITUDE EXPOSURE

Background Endothelin-1 is involved in chronic pulmonary hypertension. Its role in acute pulmonary hypertension due to hypoxia in humans is not clear. We therefore studied the influence of hypoxia caused by exp osure to high altitude on plasma endothelin-1 levels, arterial blood g ases, and pulmonary arterial pressure in subjects taking nifedipine or placebo. Methods and Results Twenty-two healthy volunteers were inves tigated at low altitude (490 m) and high altitude (4559 m). Arterial b lood gases were analyzed immediately, endothelin-1 was measured by rad ioimmunoassay, and pulmonary artery pressure was assessed by Doppler e chocardiography. After baseline investigations, the mountaineers were allocated in a randomized double-blind fashion to receive either place bo or nifedipine (20 mg TID) during rapid ascent to high altitude with in 22 hours. Tests were repeated at the high-altitude research laborat ories located in the Capanna ''Regina Margherita'' (Italy, 4559 m). Pl asma endothelin-1 was increased twofold at high altitude (5.9+/-2.2 pg /mL compared with 2.9+/-1.1 pg/mL, P<.05), was inversely related to ar terial PO2 (r=-.46, P<.001), and correlated with pulmonary artery pres sure (r=.52, P<.002). At high altitude, arterial endothelin-1 was lowe r (4.3+/-1.6 pg/mL) than venous endothelin-1 (5.9+/-2.2 pg/mL, P<.001) , indicating either predominant production in the venous vasculature o r pronounced clearance in the pulmonary circulation. The calcium antag onist nifedipine, which lowered pulmonary artery pressure at high alti tude (32+/-5 versus 42+/-11 mm Hg, P<.05), had no influence on plasma endothelin-1 levels. The administration of 35% O-2 at high altitude no rmalized arterial PO2, tended to decrease endothelin-1, and decreased pulmonary artery pressure accordingly. Conclusions We conclude that pl asma endothelin-1 is increased at high altitude, but whether or not it represents an important pathogenetic factor for pulmonary hypertensio n remains to be investigated.