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

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 42; no. 5; pp. 962 - 967
• Main Authors: Mayan, Haim, Ni, Xi-Ping, Almog, Shlomo, Humphreys, Michael H
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.11.2003; Hagerstown, MD Lippincott
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Atrial Natriuretic Factor - blood; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Bromocriptine - pharmacology; Cardiology. Vascular system; Dopamine Agonists - pharmacology; Dopamine Antagonists - pharmacology; Experimental diseases; gamma-MSH - antagonists & inhibitors; gamma-MSH - blood; gamma-MSH - pharmacology; Haloperidol - pharmacology; Hypertension - chemically induced; Hypertension - metabolism; Hypertension - physiopathology; Infusions, Intravenous; Male; Medical sciences; Pituitary Gland, Posterior - chemistry; Rats; Rats, Sprague-Dawley; Renin - blood; Sodium - urine; Sodium Chloride - toxicity; Pharmacologic test; Agonist; Rat; Bromocriptine; Pathogenesis; Peptide hormone; Cardiovascular disease; hypertension, sodium-dependent; Salt; natriuretic peptides; Regulation(control); Blood pressure; Hypertension; pituitary; Pathophysiology; Secretion; Rodentia; Ergot derivatives; γ-Melanocyte stimulating hormone; Antiparkinson agent; Pituitary hormone; Vertebrata; Sensitivity; Mammalia; D2 Dopamine receptor; Animal; Dopamine agonist; dopamine
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000097601.83235.F8

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.