THE EFFECTS OF OPIOID-PEPTIDES ON CARDIOVASCULAR FUNCTION AND SYMPATHETIC NEUROTRANSMISSION IN RATS

The haemodynamic effects of three opioid receptor agonists, with some preferential activity on delta-, mu- and kappa-receptors were investig ated in anaesthetized and pithed rats, and effects on sympathetic neur otransmission were also investigated in pithed rats. In anaesthetized rats, D-Ala(2)-D-Leu(5)-enkephalin (DADLE) (a predominantly delta-rece ptor agonist, 10 mu gkg(-1)), glyol (mu, 0.5 mgkg(-1)) and enylacetami no-2-C3-carboxy-phenylethyl-pyrrolidine (ICI 204448) (kappa, 0.1 mgkg( -1)) by intravenous administration transiently decreased heart rate fr om 462 +/- 12 to 432 +/- 14, 460 +/- 12 to 448 +/- 13 and 460 +/- 12 t o 448 +/- 11 beats min(-1), respectively, and mean arterial blood pres sure from 142 +/- 6 to 111 +/- 9, 141 +/- 6 to 122 +/- 5 and 148 +/- 7 to 121 +/- 6 mmHg, respectively. The effects of DADLE, but not those of glyol or ICI 204448, were blocked by M8008, a delta-receptor antago nist. In pithed rats, none of the opioid agonists had any significant effects on heart rate or mean arterial blood pressure; however, acetyl choline significantly reduced both heart rate and mean arterial blood pressure. All three opioid agonists reduced the positive chronotropic response to thoracic (C7-T2) spinal cord stimulation in pithed rats, b y 17 +/- 4, 30 +/- 2 and 20 +/- 10% for DADLE, glyol and ICI 204448, r espectively. This compared with a 48 +/- 15% reduction with clonidine (5 mu gkg(-1)). This effect of DADLE was almost abolished by M8008. It is concluded that the haemodynamic effects of the opioid agonists stu died are mediated via actions on the central nervous system and that a decrease in sympathetic neurotransmission may account for, at least i n part, the bradycardia produced by opioid agonists in intact anaesthe tized rats. It seems that the sympathetic nervous system is unlikely t o be involved in the arrhythmogenic effects of opioid peptides.