Peripheral sympatho-inhibitory cardiovascular effects of opioid peptides in anaesthetized rabbits.

1. Opioid agonists influence isolated cardiovascular tissues from rabbits, as well as the cardiovascular system of pithed rabbits, through presynaptic receptors on postganglionic sympathetic nerve fibres. The present experiments were carried out in order to study effects which result from activation of these receptors in anaesthetized rabbits. 2. In pithed rabbits with electrically stimulated sympathetic outflow, infusion of [D-Ala2-D-Leu5]-enkephalin (DADLE) 10 micrograms kg-1 min-1 and dynorphin-(1-13) (dynorphin) 1 microgram kg-1 min-1 decreased the plasma noradrenaline concentration, mean arterial pressure (MAP) and heart rate. The effects of dynorphin and, less completely, those of DADLE were antagonized by the peripherally selective opioid antagonists N-methyl naloxone bromide (NMN) 1.3 mg kg-1 and N-methyl levallorphan methanesulphonate (NML) 1-3 mg kg-1. 3. In pentobarbitone-anaesthetized rabbits, DADLE 3-30 micrograms kg-1 min-1 and dynorphin 0.3-3 micrograms kg-1 min-1 decreased the plasma noradrenaline concentration and MAP. The highest dose of dynorphin also decreased heart rate, whereas DADLE 10 micrograms kg-1 min-1 caused slight cardioacceleration. The effects of DADLE but not those of dynorphin decreased upon repeated administration. 4. The effects of dynorphin 10 micrograms kg-1 min-1 were abolished or greatly attenuated by NMN 1.3 mg kg-1 and NML 3 mg kg-1. In contrast, the antagonists reduced only slightly the blood pressure-lowering effect of DADLE 10 micrograms kg-1 min-1 and did not reduce significantly the effects of DADLE on the plasma noradrenaline level and heart rate. 5. It was concluded that systemically administered dynorphin produces sympatho-inhibition and an ensuing fall in blood pressure by an action at peripheral receptors, in all probability presynaptic Kappa-receptors on postganglionic sympathetic nerve fibres. The effects of DADLE are more complex and may involve both central and peripheral components.