Opioid Peptides and Central Control of Blood Pressure

Abstract

The role of endogenous opioids in central modulation of baroreceptor reflex function has been assessed in rabbits and in man using stable enkephalin analogues and synthetic opiates with a range of mu, delta and kappa opiate receptor agonist specificity. In addition the effects of naloxone, a mu opiate receptor antagonist, have been studied. In rabbits descarboxy-leu-enkephalin (RX783016) given by intracisternal injection reduced baroreflex sensitivity as assessed by heart rate responses to phenylephrine, sodium nitroprusside and controlled haemorrhage. These effects were prevented by intravenous naloxone. Naloxone alone increased the slope of the heart period: mean arterial pressure relationship and thus increased baroreflex sensitivity. In conscious man essentially similar results were found following intravenous dosing with a stable met-enkephalin analogue (DAMME, FK33824) or naloxone with decreases and increases respectively in the sensitivity of baroreflex responses to sodium nitroprusside. In rabbits and man arterial baroreceptor reflexes mediating heart rate responses can be pharmacologically modified by exogenous opiates and may be under some tonic endogenous opiate peptide influences.

Key Words:

• Opioids
• enkephalins
• blood pressure
• baroreceptor reflex
• central nervous system