Key result
High-dose intravenous beta-endorphin significantly reduced blood pressure and systemic vascular resistance in hypertensive patients (P<0.0001), effects that were annulled by naloxone.
Why the study?
Does high-dose beta-endorphin infusion reduce blood pressure and alter hormonal profiles in healthy and hypertensive subjects?
RCT (n=23)
Double-blind
Randomized
Does high-dose beta-endorphin infusion reduce blood pressure and alter hormonal profiles in healthy and hypertensive subjects?
High-dose beta-endorphin induces hypotensive and beneficial hormonal effects mediated by opioid receptors, which are enhanced in patients with essential hypertension.
Validates opioid receptor mediation of hypotensive effects; extends mechanistic RCT evidence in hypertension but leaves therapeutic translation open.
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.
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Cozzolino et al. (2005) conducted an RCT in Essential hypertension (n=23). beta-endorphin vs. beta-endorphin preceded by naloxone (8 mg) was evaluated on Hemodynamic and hormonal measurements (p=<0.0001). High-dose intravenous beta-endorphin significantly reduced blood pressure and systemic vascular resistance in hypertensive patients (P<0.0001), effects that were annulled by naloxone.
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