Acute pressor and hormonal effects of beta-endorphin at high doses in healthy and hypertensive subjects: role of opioid receptor agonism.
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.
Cozzolino
Domenico
D
Cardiovascular Research Center, II University of Naples, via Pansini, 5, 80131 Napoli, Italy. cozzolino_domenico@libero.it
Sasso
Ferdinando C
FC
Cataldo
Donato
D
Gruosso
Domenico
D
Giammarco
Armando
A
Cavalli
Antonella
A
Di Maggio
Cristiana
C
Renzo
Giuseppe
G
Salvatore
Teresa
T
Giugliano
Dario
D
Torella
Roberto
R
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
D006728:Hormones; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; D001615:beta-Endorphin