The effect of chronic administration of indomethacin in captopril-treated renal hypertensive rats.
To examine the possible involvement of prostaglandins (PG) in the antihypertensive action of captopril, a PG synthetase inhibitor (indomethacin) was administered to normal and one-kidney renovascular hypertensive rats treated with captopril for 2 weeks. Continuous infusion of captopril (40 micrograms/hr SC) to normal and renal hypertensive (RH) rats via an implantable osmotic pump for 14 days lowered systolic blood pressure (SBP) in RH rats only. However, administration of indomethacin (5 mg/kg SC) 3 times a week to normotensive rats pre-treated with captopril by continuous infusion (40 micrograms/hr SC), lowered SBP significantly 24 hours after the injection of indomethacin. In RH rats pre-treated with captopril, subsequent administration of indomethacin further reduced SBP. In this study, indomethacin given alone to both RH and normal rats produced no significant alteration in SBP. However, indomethacin potentiated the hypotensive effect of captopril. This action may be attributed to inhibition of PG biosynthesis. It has been reported that the effects of PGE2 within the kidneys are species dependent and in the case of the rat, cause vasoconstriction of the renal vasculature. Therefore, administration of indomethacin would attenuate the vasoconstricting effects of PGE2 and thus lower blood pressure. Accordingly, based on these observations, PGs may perhaps play a role in mediating the hypotensive effect of captopril.
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Department of Pharmacology, Temple University School of Pharmacy, Philadelphia, Pennsylvania 19140.
Gautieri
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Lemke
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006977:Hypertension, Renal / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology*; D007705:Kinins / Q000097:blood; D008297:Male; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects
D007705:Kinins; D011453:Prostaglandins; D002216:Captopril; D007213:Indomethacin