The effect of mu, delta, kappa and epsilon opioid receptor agonists on heart rate and blood pressure of the pithed rat.

Opioid peptides and opioid receptors are found in the hearts of various species. Opioid peptides were also shown to modulate norepinephrine inducing changes in atrial rate, in vitro. Since we have recently shown a predominance of kappa and delta receptors in the rat atria, we found it of interest to study the role of highly selective opioid agonists on spontaneous and sympathetically stimulated heart rate. The pithed, artificially ventillated rat was used in these studies. D-Ala2-D-Leu5-enkephalin (DADL), was used as an delta-agonist, D-Ala2-MePhe4-Gly-ol5-enkephalin (DAGO) as a highly selective mu-agonist; Dynorphin A (1-17) as a kappa-agonist and beta-endorphin (beta-END) as a mixed epsilon-delta-mu agonist. Naloxone was used as an opiate antagonist. None of the above opioid peptides changed the basal blood pressure and heart rate at 1-100 nmol/kg except Dyn A-(1-17) which produced a brief depressor response (-15 +/- 2 mmHg, p less than 0.01). Stimulation of the spinal cord (50 v, 1 msec, 1 Hz, 30 sec) produced consistant pressor and cardiac accelerating responses. None of the opioid peptides studied blocked or enhanced the increase in blood pressure or heart rate produced by spinal cord stimulation. The depressor effect of the high dose of Dyn A-(1-17) was not blocked by naloxone. These results suggest that mu, delta or kappa opioid receptors in the rat heart have no role in the regulation of basal or sympathetically driven heart rate. Our data also suggest no role for these opioid receptors in modulation of basal arterial tone or norepinephrine-induced arteriolar constriction.