Suppression of gamma-melanocyte-stimulating hormone secretion is accompanied by salt-sensitive hypertension in the rat.
Gamma-melanocyte-stimulating hormone (gamma-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 gamma-MSH response to a HSD. In vehicle-treated rats, plasma gamma-MSH and NIL gamma-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 gamma-MSH and NIL gamma-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 gamma-MSH nor NIL gamma-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 gamma-MSH (0.4 pmol/min) to bromocriptine-treated rats on the HSD restored plasma gamma-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 gamma-MSH normally occurring during ingestion of the HSD are prevented by dopaminergic suppression of NIL function. This results in deficiency of gamma-MSH on the HSD and is accompanied by elevated blood pressure, which is corrected by infusion of the peptide. gamma-MSH may be an important component in the normal response to a HSD; interruption of this response leads to salt-sensitive hypertension.
Institute of Clinical Pharmacology and Toxicology, Chaim Sheba Medical Center, Tel-Aviv University, Israel.
Haim
H
Mayan
Xi-Ping
XP
Ni
Shlomo
S
Almog
Michael H
MH
Humphreys
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D010904:Pituitary Gland, Posterior / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D012965:Sodium Chloride / Q000633:toxicity*; D019825:gamma-MSH / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D019825:gamma-MSH; D001971:Bromocriptine; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D012964:Sodium; D012083:Renin; D006220:Haloperidol