No evidence on significant roles of the prostaglandin-thromboxane and kallikrein-kinin system in the antihypertensive effect of MK 421 in rats made hypertensive by norepinephrine or vasopressin.

Inhibition of angiotensin converting enzyme by MK 421 (6 mg/kg/day ip) induced a significant increase in urinary kinin excretion in norepinephrine-infused rats (1.8 mg/kg/day ip), whereas it had no effect on urinary prostaglandin E2 excretion. In contrast, MK 421 did not induced any significant changes in urinary kinin and prostaglandin E2 excretion in vasopressin-infused rats (7.2 U/kg/day ip). The simultaneous administration of indomethacin (10 mg/kg/day sc), OKY 046 (12 mg/kg/day sc) or aprotinin (100,000 units/kg/day sc) did not affect the antihypertensive effect of MK 421 in rats made hypertensive by chronic infusion of norepinephrine or vasopressin. The present results suggest that the hypotensive effect of MK 421 may depend on a reduced sensitivity of the vasculature to vasoconstrictor substances. In addition, it is also suggested that neither the prostaglandin-thromboxane or kallikrein-kinin systems are essential for the antihypertensive effect of MK 421 in these models of hypertension.