Attenuation of the antihypertensive effect of captopril by the opioid receptor antagonist naloxone

Abstract

To test a possible role of endogenous opioids in the blood pressure (BP) and heart rate (HR) responses to the converting enzyme inhibitor captopril in man, nine normal subjects were given captopril (50 mg) or placebo with and without the opioid antagonist naloxone (0.2 mg/kg i.v.). Treatments were given in random order and under double-blind conditions. BP and HR were measured supine and after a 5 min head-up tilt to 60 degrees before, 90, and 360 min after captopril. BP and HR responses to Valsalva's manoeuvre and isometric exercise (sustained hand grip) were also measured, as indirect tests of baroreceptor reflex function. After captopril alone, there was a significant decrease in supine diastolic and tilt systolic and diastolic BP at 90 min (7.8, s.d. = 6; 15.4, s.d. = 13; and 7.0, s.d. = 12 (s.d. = 9), 0 (s.d. = 15) and 3 (s.d. = 7) mmHg. The effect of naloxone on the changes in supine diastolic and tilt systolic BP were significant (P = 0.017, P = 0.030 respectively; analysis of variance). No significant effects of treatment on supine or tilt HR were seen. BP and HR changes during Valsalva's manoeuvre and isometric exercise were not altered by active treatment. These results suggest that the BP but not the HR responses to converting enzyme blockade are mediated by endogenous opioids.