Peripheral sympatho‐inhibitory cardiovascular effects of opioid peptides in anaesthetized rabbits

Abstract

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 yg kg-'min-1 and dynorphin-l-13) (dynorphin) 1 pgkg-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) 1.3mgkg-1 and N-methyl levallorphan methanesulphonate (NML) 1-3 mg kg-.3 In pentobarbitone-anaesthetized rabbits, DADLE 3-30ygkg-1 min-1 and dynorphin 0.3-3 g kg -1 min-1 decreased the plasma noradrenaline concentration and MAP. The highest dose of dynorphin also decreased heart rate, whereas DADLE l0ygkg-'min-' caused slight cardioacceleration. The effects of DADLE but not those of dynorphin decreased upon repeated administration. 4 The effects of dynorphin 10pgkg-'min-' were abolished or greatly attenuated by NMN 1.3mgkg-' and NML 3mgkg-'. In contrast, the antagonists reduced only slightly the blood pressure-lowering effect of DADLE 10pgkg-min-' 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 K-receptors on postganglionic sympathetic nerve fibres. The effects of DADLE are more complex and may involve both central and peripheral components.

Personalized Nanotherapy by Specifically Targeting Cell Organelles To Improve Vascular Hypertension

“…Fenoldopam has also been shown to inhibit α 1 -and α 2 -adrenergic receptors. 24,25 Blocking of α 1 -adrenergic receptors results in a side effects of tachycardia, among others. Blocking of α 2 -adrenergic receptors in the nervous system will also result in tachycardia.…”