Effect of prolyl-leucyl-glycinamide on blood pressure, heart rate and angiotensin converting enzyme activity in spontaneously hypertensive and Wistar-Kyoto normotensive rats.

The effect of melanotropin release inhibiting factor (L-prolyl-L-leucyl-glycinamide, MIF) on blood pressure and heart rate of both spontaneously hypertensive (SH) and age-matched normotensive Wistar-Kyoto (WKY) rats was investigated. A single s.c. injection of MIF at a lower dose (1 mg/kg) had no effect on the blood pressure of either SH or WKY rats when measured 1,4 and 7 hr after the injection of MIF. Higher doses of MIF (2 or 4 mg/kg), on the other hand, significantly depressed blood pressure in SH animals at 4 and 7 hr after the drug injection. However, MIF had no effect on the blood pressure of WKY rats. None of the doses of MIF had any appreciable effect on the heart rate of either SH or WKY rats. Angiotensin-converting enzyme (ACE) activity of anterior pituitary of WKY rats was significantly higher than that of SH rats. ACE activity of neurohypophysis, however, was lower in WKY rats than in SH rats. No change in the ACE activities of central and peripheral tissues (plasma, pituitary, striatum and hypothalamus) of SH rats was observed 4 hr after the administration of MIF (1, 2 or 4 mg/kg), a time at which MIF produced significant antihypertensive effect. It is concluded that MIF causes a delayed lowering of blood pressure only in the genetically hypertensive rats and that this effect is not mediated via an action on the ACE.