Prevention of Salt-Induced Hypertension by an Analog of γ-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 γ-melanocyte-stimulating hormone (γ-MSH). Methods To study the time course, and establish the causal role, of γ-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 γ-MSH ([Nle3, D-Phe6]-γ-MSH, NDP-γ-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-γ-MSH-treated animals by Day 4, and reached a stable plateau of 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-γ-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 γ-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.