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

Abstract

γ-Melanocyte–stimulating hormone (γ-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 γ-MSH response to a HSD. In vehicle-treated rats, plasma γ-MSH and NIL γ-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 γ-MSH and NIL γ-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 γ-MSH nor NIL γ-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 γ-MSH (0.4 pmol/min) to bromocriptine-treated rats on the HSD restored plasma γ-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 γ-MSH normally occurring during ingestion of the HSD are prevented by dopaminergic suppression of NIL function. This results in deficiency of γ-MSH on the HSD and is accompanied by elevated blood pressure, which is corrected by infusion of the peptide. γ-MSH may be an important component in the normal response to a HSD; interruption of this response leads to salt-sensitive hypertension.