Beta-adrenergic blockade increases pulmonary vascular resistance and causes exaggerated hypoxic pulmonary vasoconstriction at high altitude: a physiological study

Abstract

Background An increasing number of hypertensive persons travel to high altitude (HA) while using antihypertensive medications such as beta-blockers. Nevertheless, while hypoxic exposure initiates an increase in pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR), the contribution of the autonomic nervous system is unclear. In animals, beta-adrenergic blockade has induced pulmonary vasoconstriction in normoxia and exaggerated hypoxic pulmonary vasoconstriction (HPV) and both effects were abolished by muscarinic blockade. We thus hypothesized that in humans, propranolol (PROP) increases Ppa and PVR in normoxia and exaggerates HPV, and that these effects of PROP are abolished by glycopyrrolate (GLYC). Methods In seven healthy male lowlanders, Ppa was invasively measured without medication, with PROP and PROP + GLYC, both at sea level (SL, 488 m) and after a 3-week sojourn at 3454 m altitude (HA). Bilateral thigh-cuff release manoeuvres were performed to derive pulmonary pressure-flow relationships and pulmonary vessel distensibility. Results At SL, PROP increased Ppa and PVR from (mean ± SEM) 14 ± 1 to 17 ± 1 mmHg and from 69 ± 8 to 108 ± 11 dyn s cm−5 (21% and 57% increase, P = 0.01 and P < 0.0001). The PVR response to PROP was amplified at HA to 76% (P < 0.0001, P[interaction] = 0.05). At both altitudes, PROP + GLYC abolished the effect of PROP on Ppa and PVR. Pulmonary vessel distensibility decreased from 2.9 ± 0.5 to 1.7 ± 0.2 at HA (P < 0.0001) and to 1.2 ± 0.2 with PROP, and further decreased to 0.9 ± 0.2% mmHg−1 with PROP + GLYC (P = 0.01).