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

J Clin Endocrinol Metab. 2005 Sep;90(9):5167-74. doi: 10.1210/jc.2004-2554. Epub 2005 Jun 14.

Abstract

Context: The opioid system is involved in blood pressure regulation in 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 beta-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 beta-endorphin (250 mug/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 beta-endorphin, norepinephrine, and endothelin-1 in hypertensive patients were significantly (P < 0.05) higher than in controls. In controls, beta-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, beta-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 beta-endorphin in hypertensive patients were significantly (P < 0.0001) greater than in controls but were annulled in all individuals when naloxone preceded beta-endorphin infusion.

Conclusions: High doses of beta-endorphin induce hypotensive and beneficial hormonal effects in humans, which are enhanced in essential hypertension and are mediated by opioid receptors.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Pressure / drug effects*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Hemodynamics / drug effects
  • Hormones / blood*
  • Humans
  • Hypertension / blood
  • Hypertension / drug therapy*
  • Hypertension / physiopathology*
  • Male
  • Middle Aged
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Receptors, Opioid / agonists*
  • beta-Endorphin / administration & dosage*
  • beta-Endorphin / therapeutic use

Substances

  • Hormones
  • Narcotic Antagonists
  • Receptors, Opioid
  • Naloxone
  • beta-Endorphin