Central α-melanocyte-stimulating hormone acts at melanocortin-4 receptor to activate sympathetic nervous system in conscious rabbits

Intracerebroventricular injection of α-melanocyte-stimulating hormone (α-MSH) elicited increases in arterial pressure and renal sympathetic nerve activity in conscious rabbits. Pretreatment with intracerebroventricular injection of agouti-related protein, an endogenous melanocortin-3 and 4 receptor antagonist, prevented cardiovascular and sympathetic responses to α-MSH. Pretreatment with intracerebroventricular injection of JKC-363, a synthetic specific melanocortin-4 receptor antagonist, also prevented cardiovascular and sympathetic responses to α-MSH. In contrast, intravenous α-MSH (1 nmol) failed to cause any cardiovascular responses. These results suggest that intracerebroventricularly administered α-MSH acts at the melanocortin-4 receptor in the brain and activates sympathetic outflow, resulting in an increase in arterial pressure.