Cardiovascular and endocrine effects of naloxone compared in normotensive and hypertensive patients.

Naloxone, a competitive antagonist of opioid receptors, and placebo (dextrose 5% in water (D5W) were administered on separate days to healthy normotensive (NT) male volunteers and to male patients with essential hypertension (HT). A single-blind, placebo-controlled, cross-over design was employed. Increasing doses of naloxone (0.4, 1.2, 3.6, 10.8, 32.4, 97.2 mg) were given every 30 min as slow i.v. boluses. On a separate day, i.v. boluses of D5W were given according to a similar protocol. Naloxone failed to significantly modify systolic and diastolic blood pressure (BP), heart rate (HR), respiratory rate, oral temperature or plasma catecholamines. No adverse reactions or behavioral effects were seen with naloxone. Naloxone produced a dose-dependent increase in plasma cortisol, whereas plasma cortisol showed a gradual decline on the placebo day (circadian variation). HT and NT showed similar maximal increases in plasma cortisol. Hypertensives responded to lower doses of naloxone with greater increases in plasma cortisol. The results were significantly different only if corrected by using the baseline values obtained on the placebo day. The study suggests that in awake, resting men, endogenous opioids play no role in regulating BP, HR, respiration, temperature or the activity of the sympathetic nervous system. It also suggests that the sustained elevation of BP in HT is not due to endogenous opioid substances. However, endogenous opioid substances produce a tonic inhibitory effect on the release of cortisol. This tonic inhibition seems to be greater in hypertensives than in normotensives.