Negative inotropic and chronotropic effects of delta-opioid receptor antagonists are mediated via non-opioid receptors.

Ten-minute perfusion of intact isolated rat heart with Krebs-Henseleit solution containing delta-opioid receptor agonists (DPDPE, (-)-TAN-67) or delta-opioid receptor antagonists (naltrindole, TIPP[psi], ICI 174,864) at a final concentration of 0.1 mg/liter decreased HR, blood pressure in the left ventricle, and the rates of myocardial contraction and relaxation. Intravenous injection of delta-agonists (DPDPE, (-)-TAN-67, deltorphin II) or delta-antagonists (naltrindole, TIPP[psi], ICI 174,864) decreased HR in narcotized rats. Naloxone and naltrexone produced no effect on contractility and HR both in vivo and in vitro. Preliminary injection of naloxone and naltrexone did not prevent the negative chronotropic effect of ICI 174,864 in vitro. The negative inotropic and chronotropic effects of delta-opioid receptor antagonists are mediated by unknown non-opioid receptors in the heart.