Suppression of -Melanocyte–Stimulating Hormone Secretion Is Accompanied by Salt-Sensitive Hypertension in the Rat

-Melanocyte–stimulating hormone ( -MSH) is a natriuretic peptide derived from proopiomelanocortin (POMC) in the pituitary neurointermediate lobe (NIL); its plasma concentration in rats doubles after ingestion of a high (HSD; 8% NaCl) compared with a low sodium diet (LSD; 0.07%). Because NIL function is regulated through dopaminergic pathways, we asked whether dopaminergic stimulation with bromocriptine (5 mg/kg IP daily for 1 week) or inhibition with haloperidol (5 mg/kg IP for 1 week) alters the -MSH response to a HSD. In vehicle-treated rats, plasma -MSH and NIL -MSH content on the HSD were both markedly elevated over values in rats on the LSD (P 0.001); no difference in mean arterial pressure (MAP) occurred. In haloperidol-treated rats on the LSD, both plasma -MSH and NIL -MSH content were greater than in vehicle-treated rats (P 0.05) and did not increase further on the HSD; MAP was also no different. In bromocriptine-treated rats, neither plasma -MSH nor NIL -MSH content increased on the HSD versus LSD, and MAP was markedly elevated on the HSD (132 3 versus 106 3 mm Hg, P 0.001). Intravenous infusion of -MSH (0.4 pmol/min) to bromocriptine-treated rats on the HSD restored plasma -MSH concentration to a level appropriate for the HSD and lowered MAP from 131 6 to 108 5 mm Hg (P 0.01). These results demonstrate that the increases in NIL content and plasma concentration of -MSH normally occurring during ingestion of the HSD are prevented by dopaminergic suppression of NIL function. This results in deficiency of -MSH on the HSD and is accompanied by elevated blood pressure, which is corrected by infusion of the peptide. -MSH may be an important component in the normal response to a HSD; interruption of this response leads to salt-sensitive hypertension. (Hypertension. 2003;42:962-967.)