Introduction
Altitude and dynamic exercise both increase arterial blood pressure (BP).1 2 This information is of increasing relevance to standard clinical practice given the increasing numbers of individuals with pre-existing cardiovascular conditions (eg, hypertension) sojourning at high altitude.3 Moreover, BP management is essential in the high-altitude setting since pulmonary hypertension can precipitate the development of high altitude pulmonary oedema (HAPE).4 The worrying symptomology of HAPE, including fatigue, dyspnoea and the potential for death, has made prophylaxis and treatment an important aspect of modern altitude medicine.5 The antihypertensive actions of nifedipine and dexamethasone have been shown to decrease arterial BP (although not consistently6), pulmonary artery pressure, and reduce the incidence of HAPE.6 7
Pharmacological inhibition of the renin-angiotensin-aldosterone system (RAAS) could also be beneficial for HAPE prevention and may also improve exercise performance at altitude. Support for how RAAS inhibition may prevent HAPE lies within genetic studies, which have demonstrated that genetic polymorphisms among RAAS-associated candidate genes are related with the physiologic response to hypoxic exposure.8 9 For example, polymorphisms in the ACE gene (eg, I/I vs D/D genotype) appear to partly contribute to the heterogeneity displayed in the susceptibility to high-altitude illness.10 Further, the I allele is more frequently found in climbers who successfully reach over 8000 m and has been associated with the ability to maintain higher arterial oxygenation at altitude, a greater hypoxic ventilatory drive, higher endurance performance at sea level, as well as better high-altitude adaptation.8 10 11 Parati et al have previously demonstrated the anti-hypertensive effects of RAAS inhibition (via telmisartan, 80 mg dose) during exposure to high altitude,12 however, the potential of RAAS inhibition to improve exercise performance at altitude remains unknown, as does its ability to reduce exercise-induced evidence of pulmonary hypertension (eg, increases in extravascular lung water (EVLW)).13 Interestingly, Kiely et al reported that losartan, an angiotensin II receptor antagonist, reduced both systemic BP and pulmonary vascular resistance in response to acute graded hypoxic exposure.14 Whether this laboratory-based observation translates to the sustained hypoxic exposure of the high-altitude setting remains to be determined.
Therefore, the purpose of this study was to evaluate the effects of the angiotensin II receptor antagonist, losartan, on BP during ascent and to determine whether it could improve exercise performance at 5035 m. We hypothesised that blockade of the angiotensin receptor would reduce altitude-related increases in resting and exercising BP, reduce the effect of strenuous exercise on the development of EVLW at high altitude, and ultimately improve exercise performance via enhanced pulmonary ventilation (VE)-perfusion matching and increased arterial oxygenation.