Prevention of salt-induced hypertension by an analog of gamma-melanocyte-stimulating hormone in the rat.
BACKGROUND
Rats with suppression of pituitary intermediate lobe (IL) function by treatment with the dopaminergic agonist bromocriptine develop salt-sensitive hypertension accompanied by a deficiency of gamma-melanocyte-stimulating hormone (gamma-MSH).


METHODS
To study the time course, and establish the causal role, of gamma-MSH deficiency in the development of salt-sensitive hypertension, we instrumented 12 male Sprague-Dawley rats with radiotelemetry transmitters to record intraaortic mean arterial pressure (MAP). One week later, they were placed on a high-sodium diet (8% NaCl, HSD) and received daily intraperitoneal injections of bromocriptine (5 mg/kg). The rats were also implanted with micro-osmotic pumps to deliver either a stable analog of gamma-MSH ([Nle3, D-Phe6]-gamma-MSH, NDP-gamma-MSH) at 12 pmol/h or normal saline vehicle.


RESULTS
In vehicle-treated rats on the HSD and receiving bromocriptine injections, MAP rose so that it was significantly greater than that in NDP-gamma-MSH-treated animals by Day 4, and reached a stable plateau of approximately 135 mm Hg between Days 7 and 14. After Day 14, bromocriptine injections were stopped, and MAP in vehicle-infused rats fell progressively despite continued ingestion of the HSD, so that by Day 18, MAP was no longer different from NDP-gamma-MSH-infused animals. The MAP in the latter group did not vary significantly from the control level of 101+/-4 mm Hg throughout the 21 days of the experiment.


CONCLUSIONS
These results indicate that gamma-MSH deficiency is a consequence of the bromocriptine treatment responsible for the salt-sensitive hypertension, and these results also identify the time course during which this hypertension develops.
Ni
Xi-Ping
XP
Division of Nephrology, San Francisco General Hospital, and Department of Medicine, University of California at San Francisco, San Francisco, California 94143, USA.
Humphreys
Michael H
MH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001795:Blood Pressure Determination / Q000379:methods; D001971:Bromocriptine / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D005500:Follow-Up Studies; D006728:Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D015918:Infusion Pumps, Implantable; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000633:toxicity; D013686:Telemetry; D016896:Treatment Outcome; D019825:gamma-MSH / Q000008:administration & dosage / Q000627:therapeutic use*
D018491:Dopamine Agonists; D006728:Hormones; D017673:Sodium Chloride, Dietary; D019825:gamma-MSH; D001971:Bromocriptine