Acute pressor and hormonal effects of beta-endorphin at high doses in healthy and hypertensive subjects: role of opioid receptor agonism.

Context: The opioid system is involved in blood pressure regulationin both normal humans and patients with essential hypertension. Objective: The objective of the study was to investigate the effects of a high-dose infusion of *-endorphin, an opioid peptide, on blood pressure and on the hormonal profile in healthy subjects and in hypertensive patients and the mediation played by opioid receptor agonism. Design, Setting, and Participants: According to a randomized double- blind design, 11 healthy subjects (controls) and 12 hypertensive inpatients(mean age, 38.9 and 40.4 yr, respectively) received 1-h iv infusion of *-endorphin (250 *g/h) and, on another occasion, the same infusion protocol preceded by the opioid antagonist naloxone (8 mg). Main Outcome Measures: Hemodynamic and hormonal measurements were performed at established times during the infusion protocols. Results: At baseline, circulating *-endorphin, norepinephrine, and endothelin-1 in hypertensive patients were significantly (P * 0.05) higher than in controls. In controls, *-endorphin reduced blood pressure(P * 0.01) and circulating norepinephrine (P * 0.02) and increased plasma atrial natriuretic factor (P * 0.003) and GH (P * 0.0001). In hypertensive patients, *-endorphin decreased systemic vascular resistance (P * 0.0001), blood pressure (P * 0.0001), and plasma norepinephrine (P * 0.0001) and endothelin-1 (P * 0.0001) and raised circulating atrial natriuretic factor (P * 0.0001), GH (P * 0.0001), and IGF-I (P * 0.0001). These hemodynamic and hormonal responses to *-endorphin in hypertensive patients were significantly (P * 0.0001) greater than in controls but were annulled in all individuals when naloxone preceded *-endorphin infusion. Conclusions: High doses of *-endorphin induce hypotensive and beneficial hormonal effects in humans, which are enhanced in essential hypertension and are mediated by opioid receptors