SUMMARY We describe two studies designed to elucidate the role of endogenous opioids in blood pressure control in humans. In the first study, nine normal subjects received infusions of DAMME (a metenkephalin analog), naloxone, or saline, and blood pressure, heart rate, and plasma norepinephrine concentration were determined supine and following 5 minutes of 70° head-up tilt at intervals for 6 hours. Blood pressure following tilt was significantly decreased by DAMME but not influenced by naloxone, the effect being most marked at 3 hours (placebo = 110 ± 6/78 ± 7 mm Hg; naloxone = 106 ± 10/79 ± 5 mm Hg; DAMME = 96 ± 16/67 ± 8 mm Hg (p < 0.01). However, heart rate and plasma norepinephrine did not rise in response to this hypotension. Heart rates at 3 hours were: placebo = 87 ± 16 bpm; naloxone = 88 ± 19 bpm; DAMME = 89 ± 23 bpm. Plasma norepinephrine levels (nmol/ liter) at 3 hours were: placebo = 6.0 ± 2.2; naloxone = 5.8 ± 1.9; DAMME = 6.0 ± 1.9. In the second study, seven normal subjects had blood pressure reduced by incremental infusions of sodium nitroprusside, and the effects of placebo, naloxone, and DAMME on the slope of the heart period/ blood pressure relationship investigated. Naloxone significantly increased the slope by 90% and DAMME significantly reduced the slope by 30%. It is concluded that endogenous opioids modulate the baroreflex control of blood pressure in normal humans. (Hypertension 5: 535-538, 1983) KEY WORDS • enkephalin • DAMME • naloxone • blood pressure E NDOGENOUS opioids may participate in circulatory control. Administration of synthetic opioid pentapeptides to the cisterna magna of dogs produces a fall in blood pressure.1 The specific opiate receptor antagonist, naloxone, reverses the fall in blood pressure associated with both endotoxic and hypovolemic shock in rats, 2 -3 and preliminary data suggest similar findings in humans. 4 A physiological role for opioids in blood pressure control is suggested by the observation that naloxone prevents the fall in blood pressure in humans that normally occurs during sleep.5 A possible site of opioid action is in the brain stem at primary baroreceptor synapses in the nucleus of the solitary tract. This area is known to have a high concentration of opioid containing fibers and opiate receptors.6 -7 In dogs and rabbits, the circulatory reflex responses to both pressor and depressor stimuli are attenuated by morphine or opioid analogs and potentiated by naloxone. 89 We have studied the influence on circulatory control in humans of a metenkephalin analog and of naloxone. Our findings suggest that the endogenous opioids modulate baroreflex function in humans.From the University Department of Materia Medica, Stobhill General Hospital, Glasgow Scotland.This study was supported by British Heart Foundation Grant 80/ 85.Address for reprints: Dr. Peter Rubin, University Department of Materia Medica, Stobhill General Hospital, Glasgow G21 3UW, Scotland.Received August 27, 1982; revision accepted December 6, 1982.
MethodsThe study was performed in two p...