Effect of Bosentan on Exercise Capacity at High Altitude

This study is to determine whether bosentan will alter exercise capacity after rapid ascent to high altitude. We hypothesize that bosentan administration will improve arterial oxygenation and exercise capacity.

Both the prostacyclin and the nitric oxide pathways are important in modulating hypoxic pulmonary vasoconstriction (HPV). There is little information about the role of the endothelin pathway at high altitude. The endothelin pathway involves the activation of two distinct receptors, A and B. Bosentan is a nonpeptide, specific, competitive, dual antagonist of both endothelin receptor subtypes. The primary objective of this study will be to determine the effect of endothelin receptor blockade with bosentan on exercise performance and HPV. This is a prospective, double blind, placebo-controlled, randomized cross-over study involving healthy subjects aged 25-55 years of age. Subjects will undergo echocardiography and exercise testing at low altitude (< 500m) and at 3800m. Subjects will receive either bosentan vs. placebo and will be studied at low and high altitude on two occasions in a crossover design. Primary outcome measures will be pulmonary artery systolic pressure measured by echo-Doppler and exercise capacity. A better understanding of the role of the endothelin pathway in HPV may lead to improved treatments for some patients.

Inclusion Criteria: Normal healthy subjects aged 18 - 55 years Exclusion Criteria: Pregnancy Heart, lung or liver disease Use of glyburide, cyclosporin A

Seheult RD, Ruh K, Foster GP, Anholm JD. Prophylactic bosentan does not improve exercise capacity or lower pulmonary artery systolic pressure at high altitude. Respir Physiol Neurobiol. 2009 Feb 28;165(2-3):123-30. doi: 10.1016/j.resp.2008.10.005. Epub 2008 Oct 11.