Dexamethasone-mediated modulation of the renin-angiotensin system: current insights

Dexamethasone (DEX) exerts pleiotropic effects that extend beyond classical glucocorticoid receptor signaling and include interactions with the renin–angiotensin system (RAS). Growing evidence indicates that DEX regulates both systemic and tissue-specific RAS activity through genomic and non-genomic mechanisms, affecting the expression and activity of key components, including angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), and angiotensin receptors AT1 and AT2. This mini-review summarizes current evidence on DEX-induced RAS modulation and its physiological and pathological implications. Depending on dose, duration, and biological context, DEX may exert both beneficial and adverse effects. Short-term exposure can suppress renin activity and aldosterone secretion and may provide protective effects in selected acute pathological conditions. In contrast, prolonged or high-dose treatment may promote hypertension, electrolyte imbalance, cardiac remodeling, and tissue dysfunction through dysregulation of RAS signaling. DEX also alters local RAS activity in bone, contributing to osteoporosis and osteonecrosis by enhancing osteoclast activity and impairing osteoblast function. In the kidney and lung, DEX-mediated RAS modulation affects fluid homeostasis, inflammatory responses, and susceptibility to tissue injury. Prenatal exposure to DEX may further induce long-term RAS programming, increasing the risk of cardiovascular, renal, and skeletal disorders in adulthood. Collectively, DEX–RAS interactions represent an important but often overlooked aspect of glucocorticoid pharmacology and may contribute to both the therapeutic and adverse effects of DEX.