Depressor and bradycardic effects induced by spinal subarachnoid injection of D-Ala 2-D-Leu 5-enkephalin in rats

Abstract

The effects of D-Ala 2-D-Leu 5-enkephalin (DADLE), a specific delta receptor agonist, on spinal control of cardiovascular function, were investigated by its intrathecal (i.th) injection into the spinal subarachnoid space at the T-9 level. In chloralose-anesthetized rats, DADLE (17.5, 35 and 70 nmol, i.th) caused dose-dependent hypotension and bradycardia. The mean maximal hypotension by 70 nmol of DADLE was −45 ± 7 mmHg, with a bradycardia of −79 ± 15 beats/min. These inhibitory cardiovascular effects were antagonized by the opiate antagonist naloxone (50 nmol, i.th.) given prior to DADLE. Intrathecal injection of DADLE also decreased splanchnic sympathetic nerve discharge (−46 ± 5%). DADLE (70 nmol) given i.v. did not cause significant changes in mean arterial pressure (MAP) and heart rate (HR). Neither bilateral vagotomy nor pretreatment with atropine (0.2 mg/kg, i.v.) prevented the BP and HR effects of intrathecal injection on DADLE at a dose of 35 nmol. DADLE at this dose failed to produce significant alteration in the frequency of respiration and blood PaO 2, PaCO 2 and blood pH. In conscious rats, 140 nmol of DADLE (i.th.) did not produce any consistent changes in MAP and HR. These data suggest that intrathecal injection of DADLE inhibits central sympathetic activity, possibly at a spinal locus.