Endogenous Opioids Modulate Central Nervous System Blood Pressure Control in Man

1. Two studies were performed to elucidate the role of opioids in blood pressure control in man. 2. Study 1: nine normal subjects, 18–32 years, received in a randomized single blind manner, volume matched infusions of a Met-enkephalin analogue (DAMME) 0.5 mg, naloxone 0.2 mg/kg or saline. Blood pressure, heart rate and plasma noradrenaline were determined supine and after a 5 min, 70° head-up tilt at 0, 3/4, 2, 3, 4, 5 and 6 h. 3. Study 2: seven subjects, after baseline recordings of blood pressure and heart rate received six incremental infusions of sodium nitroprusside, 1.5–7.5 μg min−1 kg−1. They then received DAMME or naloxone and the nitroprusside infusions were repeated between 3 and 4 h. There was a significant linear relationship between fall in mean arterial pressure and rise in heart rate in each case and the slope was used as an index of baroreflex sensitivity. 4. Neither naloxone nor DAMME influenced supine blood pressure or heart rate. Blood pressure after head-up tilt was significantly (analysis of variance) decreased by DAMME for up to 5 h but not by naloxone, the effect being most marked at 3 h: systolic (mean ± sd), placebo 110 ± 6, naloxone 106 ± 10, DAMME 96 ± 16 (P< 0.02); diastolic (mean ± sd), placebo 78 ± 7, naloxone 79 ± 5, DAMME 67 ± 8 (P < 0.01). The increases in heart rate and plasma noradrenaline on tilting after DAMME were not significantly different from values with placebo or naloxone. The 3 h values for heart rate were: placebo 87 ± 16, naloxone 88 ± 19, DAMME 89 ± 23 (P > 0.1); for plasma noradrenaline (nmol/l): placebo 6.0 ± 2.2, naloxone 5.8 ± 1.9, DAMME 6.0 ± 1.9 (P > 0.1). 5. Naloxone significantly increased the slope (beats per min/mmHg) of the regression relationship from a mean of 1.8 ± 0.07 to 3.0 ± 1.3 (P < 0.05), and DAMME reduced the slope from 2.7 ± 1.7 to 1.2 ± 0.5 (P < 0.05). 6. We conclude that endogenous opioids modulate baroreflex function in man.