Published Online
on October 20, 2003

A more recent version of this article appeared on November 1, 2003

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Submitted on April 29, 2003
Revised on May 27, 2003

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

Haim Mayan; Xi-Ping Ni; Shlomo Almog; and Michael H. Humphreys^*

From the Institute of Clinical Pharmacology and Toxicology (H.M., S.A.), the Department of Medicine E (H.M.), Chaim Sheba Medical Center, Tel-Aviv University, Israel; and the Division of Nephrology (X.-P.N., M.H.H.), San Francisco General Hospital, UCSF, San Francisco, Calif.

^* To whom correspondence should be addressed. E-mail: mhhsfgh{at}itsa.ucsf.edu.

Abstract---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.

Key words: natriuretic peptides • pituitary • hypertension, sodium-dependent • dopamine

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