Effects of captopril on the urinary excretion of prostanoids and kallikrein in spontaneously hypertensive rats.
The possible roles of vasodilatory prostanoids and the kallikrein-kinin system in the antihypertensive action of the angiotensin-converting enzyme (kininase II) inhibitor captopril were examined in spontaneously hypertensive rats. Captopril (20, 50 or 100 mg/kg daily orally) reduced blood pressure markedly and dose-dependently. It also increased water consumption and urine excretion, measured on the 5th day of treatment. The 24-hr urinary excretion of PGE2 was not changed, whereas that of PGF2 alpha and TxB2 tended to be enhanced. A clear increase, significant with all doses of captopril, occurred in the urinary excretion of 6-keto-PGF1 alpha. Kallikrein excretion in urine was suppressed by the two larger doses of captopril. The markedly augmented urinary excretion of 6-keto-PGF1 alpha, the stable metabolite of vasodilatory prostacyclin (PGI2), suggests that increased prostacyclin production may participate in the antihypertensive mechanism of captopril. Vasodilatory kinins can also contribute, since the captopril-induced decrease in kallikrein may reflect accumulation of kinins due to their reduced metabolism.
D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000652:urine*; D007610:Kallikreins / Q000652:urine*; D008297:Male; D011453:Prostaglandins / Q000652:urine*; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood; D013929:Thromboxane B2 / Q000652:urine
D011453:Prostaglandins; D013929:Thromboxane B2; D002216:Captopril; D007610:Kallikreins; D012083:Renin