The effect of amlodipine on respiratory and pulmonary vascular responses to hypoxia in mountaineers.

Calcium antagonists are known to reduce the incidence of high-altitude pulmonary oedema, but the mechanism is unclear. The aim of this study was to examine the effects of the calcium antagonist, amlodipine, on cardiac and respiratory responses in normoxia and hypoxia. Fourteen normal subjects aged 31+/-4 yrs who had climbed to altitudes of 5,000-7,500 m without problems were randomly assigned to a double-blind crossover trial of amlodipine versus placebo, using sea-level inspiratory hypoxia to simulate altitude. Doppler echocardiographic estimates of resting pulmonary haemodynamics and cycle ergometer test results of cardiorespiratory responses to exercise were recorded in normoxia and hypoxia. It was found that, although hypoxic pulmonary vasoconstriction (HPV) was not significantly reduced by amlodipine, the effect of the drug on HPV was inversely related to the serum level of amlodipine. Amlodipine did not alter left ventricular function measured echocardiographically. During exercise, amlodipine increased breathlessness, measured using standard scales, in both normoxia and hypoxia but had no effect on ventilatory variables. It was concluded that amlodipine has the potential to block hypoxic pulmonary vasoconstriction as evidenced by a drug concentration-related decrease in resting tricuspid regurgitation jet velocity without any change in resting myocardial contractility. However, with amlodipine, the subjects felt more breathless during exercise. The reasons for this increase in breathlessness are not clear.