Growth hormone-releasing hormone signaling and manifestations within the cardiovascular system

Growth hormone (GH)-releasing hormone (GHRH), a hypothalamic peptide initially characterized for its role in GH regulation, has gained increasing attention due to its GH-independent action on peripheral physiology, including that of the cardiovascular system. While its effects on the peripheral vasculature are still under investigation, GHRH and synthetic agonists have exhibited remarkable receptor-mediated cardioprotective properties in preclinical models. GHRH and its analogs enhance myocardial function by improving contractility, reducing oxidative stress, inflammation, and offsetting pathological remodeling. Studies performed in small and large animal models have demonstrated the efficacy of these compounds in diverse cardiomyopathies, suggesting their potential as promising therapeutic agents. However, the clinical translation of GHRH synthetic analogs still faces challenges related to the route of administration and potential side effects mainly associated with activation of the GH/IGF-I axis. Despite these hurdles, the compelling evidence supporting their role in cardiac repair makes GHRH analogs attractive candidates for clinical testing in the treatment of various cardiac diseases.