Indomethacin does not attenuate the hypotensive effect of captopril, a converting enzyme inhibitor in Goldblatt hypertensive rats.

Abstract

OMATA, K., OTSUKA, Y., CHIBA, S., ITOH, T., GOTOH, T., IMAI, Y., SAKURAI, Y., SATOH, M., HARUYAMA, T., HIWATARI, M., SATOH, K., KAITOH, A., ABE, K. and YOSHINAGA, K. Indomethacin Does Not Attenuate the Hypotensive Effect of Captopril, a Converting Enzyme Inhibitor in Goldblatt Hypertensive Rats. Tohoku J. exp. Med., 1981, 134 (1), 9-19-Whether or not prostaglandins (PGs) have anything to do with the hypotensive effect of a converting enzyme inhibitor, Captopril (SQ 14, 225), was studied in two kidney one clip Goldblatt hypertensive rats. Four to 10 weeks after clipping the left renal artery of male Splague-Dawley rats, 50mg/kg of captopril (Group 1, n=7) or 12.5mg/kg of indomethacin (Group 2, n=7) were infused for 4hr under the conscious state. For the subsequent 4hr, both 50mg/kg of captopril and 12.5mg/kg of indomethacin were infused in both groups of rats. Mean blood pressure (MBP) was recorded continuously. Plasma renin activity (PRA) and urinary excretion rate of PGE (UPGE) were measured by radioimmunoassay. Urinary sodium (UNa) and potassium (UK) excretions were measured by a flame photometer. After captopril infusion the pressor response to the injection of 100ng of angiotensin I decreased from 29.1± 4.2 to 4.8±1.6mmHg, and that of angiotensin II increased from 35.9±3.6 to 75.0±5.1mmHg (p<0.01), while the response to norepinephrine did not change. Indomethacin did not affect these pressor responses. In the preinfusion period MBP, PRA or UPGE was not different significantly in the two groups of rats. The infusion of captopril decreased MBP from 202±11 to 119±7.5mmHg (p<0.01) in the first group of rats. After the additional infusion of indomethacin MBP further decreased to 100±12mmHg, depsite the significant decrease of UPGE from 915±34 to 109±28pg/hr (p<0.01), and PRA increased from 22.1±4.2 to 34.1±7.1ng/ml/hr. UNa did not change after captopril infusion but decreased significantly after indomethacin infusion from 49.0±5.0 to 22.8±3.5μEq/hr. In the second group captopril also decreased MBP from 187±7 to 119±15mmHg (p <0.01), and increased PRA from 24.1±6.1 to 43.3±6.9ng/ml/hr (p<0.01) despite the significant decrease of UPGE from 1219±294 to 413±101pg/hr by the pretreatment with indomethacin. UNa did not change in any period. The decrease of MBP was significantly correlated with the level of PRA prior to the infusion of captopril in both groups (r=-0.69, p<0.01). UK did not change significantly in any period in the two groups of rats. Our data that indomethacin did not attenuate the hypotensive effect of captopril indicate that PGs do not participate in the hypotensive effect of captopril and that the hypotensive effect of captopril is mainly due to the inhibition of renin-angiotensin system in two kidney one clip Goldblatt hypertensive rats.