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.

The Influence of Captopril and Naloxone on the Valsalva Manoeuvre and Systolic Time Intervals in Healthy Volunteers

“…In the present study in normal volunteers, naloxone did not alter captopril-induced changes in BP and Valsalva ratio. This is in contrast to previous studies (Millar et al 1983;Rubin et al 1984;Ajayi et al 1985b) where reversal of captopril induced changes in BP and HR was abolished by naloxone, but only after 60-90 min.…”

“…Richter et al 1991) and thus possibly inhibiting sympathetic nerve stimulation, which could account for the absence of reflex tachycardia. Furthermore, attenuation of the antihypertensive effect of captopril by naloxone has been previously demonstrated (Millar et al 1983;Rubin et al 1984).…”

Prolonged severe hypotension following combined amlodipine and valsartan ingestion

“…In dogs, 0.1 mg/kg naloxone reversed enalapril and enalaprilic acid inhibition of the vagal-stimulation pressor response (40). Co-administration of 0.2 mg/kg naloxone mitigated captopril-related decreases in systolic and diastolic blood pressure in healthy men (41). Another double-blind, placebo-controlled study of healthy men found that naloxone pretreatment with 10 mg followed by 2.46 mg/hr infusion eliminated captopril-induced systolic blood pressure drop (42).…”

Drugs and pharmaceuticals: management of intoxication and antidotes

“…Naloxone has been ineffective in reversing hypotension in other cases complicated by co-ingestants [464]. The mechanism may relate to antagonism of endogenous opioids [465]. Co-administration of 0.2 mg/kg naloxone mitigated captopril-related decreases in systolic and diastolic blood pressure in healthy volunteers [465].…”

“…The mechanism may relate to antagonism of endogenous opioids [465]. Co-administration of 0.2 mg/kg naloxone mitigated captopril-related decreases in systolic and diastolic blood pressure in healthy volunteers [465]. A placebo-controlled study of healthy men found that naloxone pretreatment with 10 mg followed by 2.46 mg/hour infusion precluded systolic blood pressure decrease induced by captopril (50 mg) [466].…”