Exercise-induced Erythropoiesis: the Mechanistic of Angiotensin II

Physical activity, particularly when comprised of endurance training (ET) leading to cardiovascular adaptations, is considered the most effective intervention to augment life expectancy. Major health benefits induced by ET are closely associated (independently of traditional risk factors) with improvements in maximal oxygen consumption (VO2max), a hallmark of aerobic exercise capacity. The higher the VO2max the greater the likelihood to be free of cardiovascular disease, the main cause of mortality worldwide. Understanding the mechanisms explaining the improvement in VO2max with ET can provide sound basis for highly effective lifestyle and pharmacological interventions aimed to enhance cardiovascular health in the general population. So far, the essential role of ET-induced increased formation of red blood cells, i.e., erythropoiesis, has been firmly established for any improvement in VO2max. Yet, the underlying mechanism remains elusive. Clinical studies and recent investigations by the PI point towards the endocrine effects of key hormones that regulate blood volume (BV). Notably, the impact of ET-induced changes in angiotensin II (ANGII), a multifaceted hormone that modulates erythropoiesis through its effects on kidney erythropoietin (EPO) production, has to be experimentally elucidated in humans.