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

Abstract

Inhibition of angiotensin converting enzyme by MK 4–21 (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 induce any significant changes in urinary kinin and prostaglandin E₂ excretion in vasopressininfused 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 4–21 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.

Key Words:

• ACE inhibitors
• Angiotensin coverting enzyme
• Cyclo-oxygenase inhibitor
• Thromboxane synthetase inhibitor
• Kallikrein inhibitor