Cardiovascular responses to opioid agonists injected into the nucleus of tractus solitarius of anesthetized cats.

It has been proposed that various opiate receptor subtypes mediate different cardiovascular responses to centrally administered opioids. We evaluated this hypothesis in chloralose-urethane anesthetized cats by monitoring the cardiovascular and respiratory responses to relative mu [morphine, morphiceptin, D-Ala2, MePhe4, Gly-ol5 enkephalin (DAGO)] and delta [D-Ala2, D-Leu5enkephalin (DADL)] agonists microinjected (0.5 ul/kg) into the caudal region of the Nucleus of Tractus Solitarius (NTS). Dynorphin (1-13), an endogenous opioid which exhibits selective affinity towards the kappa receptor, was also tested. Dynorphin at a dose of 50 nMol/kg did not alter cardiovascular or respiratory variables. Morphine (10-54 nMol/kg) and DAGO (50 nMol/kg) had no effect on blood pressure, heart rate or respiratory rate; morphiceptin (100-320 nMol/kg) caused tachycardia only at the highest dose. DADL (10-100 nMol/kg) elicited a dose-dependent depression of blood pressure. High doses of DADL depressed heart rate and respiratory rate. The depressor effects of DADL were reversed by low doses of naloxone (0.1 mg/kg). This dose of naloxone also elicited pressor responses in cats treated with the other opioids and reversed the morphiceptin-induced tachycardia. These data indicate that opioid agonists differ with regard to their cardiovascular and respiratory effects following microinjection into the NTS of anesthetized cats, with the delta agonist DADL showing greatest activity.