title: Acute pressor and hormonal effects of beta-endorphin at high doses in healthy and hypertensive subjects: role of opioid receptor agonism.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
authors.affiliation: Cardiovascular Research Center, II University of Naples, via Pansini, 5, 80131 Napoli, Italy. cozzolino_domenico@libero.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Cozzolino
authors.forename: Ferdinando C
authors.initials: FC
authors.lastname: Sasso
authors.forename: Donato
authors.initials: D
authors.lastname: Cataldo
authors.forename: Domenico
authors.initials: D
authors.lastname: Gruosso
authors.forename: Armando
authors.initials: A
authors.lastname: Giammarco
authors.forename: Antonella
authors.initials: A
authors.lastname: Cavalli
authors.forename: Cristiana
authors.initials: C
authors.lastname: Di Maggio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Renzo
authors.forename: Teresa
authors.initials: T
authors.lastname: Salvatore
authors.forename: Dario
authors.initials: D
authors.lastname: Giugliano
authors.forename: Roberto
authors.initials: R
authors.lastname: Torella
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006728:Hormones / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists*; D001615:beta-Endorphin / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D006728:Hormones; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; D001615:beta-Endorphin