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.
Division of Nephrology, San Francisco General Hospital, and Department of Medicine, University of California at San Francisco, San Francisco, California 94143, USA.
Xi-Ping
XP
Ni
Michael H
MH
Humphreys
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