Renal prostaglandin E in the hypotensive mechanism of MK-421 in conscious rats.
To assess the role of renal prostaglandin E in the hypotensive mechanism of MK-421, we evaluated the effects of chronic infusion of MK-421 (6 mg/kg/day i.p.) on systolic blood pressure and urinary prostaglandin E excretion in conscious rats in states of sodium repletion or depletion and also during chronic infusion of norepinephrine (1.8 mg/kg/day i.p.) or vasopressin (7.2 U/kg/day i.p.). The hypotensive effect of MK-421 was greater in sodium depleted than in sodium repleted rats. The hypertensive effect of norepinephrine or vasopressin was inhibited by the simultaneous administration of MK-421. MK-421 induced an increase in the excretion of urinary prostaglandin E, in both sodium repleted and depleted rats. However, simultaneous administration of MK-421 had no influence on the increase in urinary prostaglandin E excretion induced by norepinephrine or vasopressin. In addition, the combined administration of MK-421 with indomethacin (10 mg/kg/day s.c.) still abolished the hypertensive effect of norepinephrine or vasopressin. The disparate effect of MK-421 on urinary prostaglandin E excretion suggests that the renal prostaglandin system is not essential for the mechanism of the hypotensive effect of MK-421.
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D004151:Dipeptides / Q000494:pharmacology*; D004656:Enalapril; D006973:Hypertension / Q000139:chemically induced / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011458:Prostaglandins E / Q000502:physiology* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000172:deficiency; D014667:Vasopressins / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004151:Dipeptides; D011458:Prostaglandins E; D014667:Vasopressins; D000804:Angiotensin II; D004656:Enalapril; D000803:Angiotensin I; D012964:Sodium; D009638:Norepinephrine