Does indomethacin pretreatment reduce the acute haemodynamic and hormonal effects of captopril in healthy men?
Indomethacin pretreatment diminishes the acute blood pressure-lowering and hormonal effects of captopril, suggesting that prostaglandins contribute to the pharmacological actions of ACE inhibitors.
The acute haemodynamic and hormonal effects of 100 mg of captopril (SQ 14.225) orally were tested in twelve healthy men in the sodium replete state before and after indomethacin pretreatment. 2. Without indomethacin, mean arterial blood pressure was reduced at 30 and 60 min after captopril (P less than 0.02). Heart rate did not change during the whole experiment. Although plasma renin activity (PRA) increased (P less than 0.002), plasma and urinary aldosterone and plasma 18-hydroxycorticosterone (18-OH-B) decreased after captopril (P less than 0.02). Prostaglandin (PG) E2, sodium and potassium excretion rates remained constant after captopril. 3. Under indomethacin pretreatment, the fall in mean arterial blood pressure was less than without indomethacin at 30 and 60 min after captopril (P less than 0.05). Heart rate was constantly lower than without indomethacin during the whole experiment (P less than 0.05). Indomethacin pretreatment decreased basal PGE2 excretion (P less than 0.02) and baseline PRA as well as the increase in PRA after captopril (P less than 0.05). Control mineralocorticoid levels were significantly lower than without indomethacin. In indomethacin-pretreated subjects, aldosterone did not further decrease after captopril, and 18-OH-B fell only slightly. 4. Without indomethacin pretreatment a significant, positive correlation was found between PRA values before captopril and the maximum decrease of mean arterial blood pressure after captopril. Under indomethacin pretreatment this correlation was no longer demonstrable. The results suggest that prostaglandins may contribute to the haemodynamic and hormonal actions of captopril.
Witzgall et al. (Tue,) studied this question.