Blockade of Angiotensin II Receptor Type 1 Abolishes the Erythropoietin Response to Exercise

Abstract Beneficial adaptations to exercise depend on the normal function of the endocrine system. Whether commonly prescribed antihypertensive medication inhibits erythropoietin (EPO) production with exercise, a key response to enhance aerobic capacity, remains unknown. Healthy adults (n = 63, 42.3 ± 16.5 yr, 52% ♀) matched by age, sex, and physical activity were randomized in a blinded and crossover manner to orally ingest valsartan (angiotensin II type 1 receptor-blockade, AT1-blockade) or placebo (calcium carbonate, PBO) 4 h before starting the experimental protocol. Before and after 1 h of moderate cycling exercise, blood samples were taken to measure circulating EPO and EPO-regulating hormones along with blood pressure. Cardiac structure/function and peak pulmonary O2 consumption (VO2peak) were assessed during exercise. AT1-blockade decreased heart volumes (left atrium and ventricle) during exercise compared with PBO, particularly in men (P ≤ 0.036). Whole-body O2 extraction and VO2peak were unaffected by AT1-blockade irrespective of sex (P ≥ 0.325). Before and after exercise, AT1-blockade reduced arterial blood pressures (systolic, diastolic) in both sexes (P < 0.001). A condition × time interaction was detected for circulating EPO (P = 0.002), such that AT1-blockade decreased EPO at 3-h post-exercise compared with PBO (P ≤ 0.025). The effect of exercise on EPO-regulating hormones (angiotensin II, aldosterone, copeptin) was diminished with AT1-blockade. Sex per se did not influence the endocrine response to AT1-blockade. In conclusion, in a randomized, double-blind and placebo-controlled study design, AT1-blockade abolishes the acute EPO response to exercise in women and men. Antihypertensive medications hindering AT1 signaling may restrict key endocrine responses to exercise.