Cardiovascular responses to κ opioid agonists in intact and adrenal demedullated rats

Abstract

The effects of three κ opioid agonists namely, bremazocine, tifluadom and U-50,488H were studied on blood pressure and heart rate in urethane-anesthetized normal and bilateral adrenal demedullated rats. Bremazocine (0.2, 0.4 and 0.6 mg/kg i.v.) produced a dose-dependent decrease in heart rate, while only 0.4 mg/kg bremazocine produced marked hypotension. The effect appeared to be long lasting because even at 60 min following drug administration the decreases in both heart rate and blood pressure continued. Bilateral adrenal demedullation did not change bremazocine- increased fall in blood pressure but the bradycardia was partially blocked. Tifluadom (0.1–0.4 mg/kg i.v.) produced an initial arrest of heart beat followed by bradycardia which recovered in about 60 min. Except for a very transient fall soon after drug administration no significant effect was observed on blood pressure. In adrenal demedullated rats, tifluadom induced initial arrest of heart was not affected but the subsequent bradycardia was blocked. U-50,488H (0.2, 0.4 and 0.6 mg/kg i.v.) produced dose-dependent bradycardia and hypotension both of which were blocked following bilateral adrenal demedullation. Naltrexone methylbromide (MRZ 2663 BR), a quaternary opioid antagonist, injected 5 min prior to U-50,488H, blocked its cardiovascular effects. The results suggest that κ opioid agonists given i.v. depress cardiovascular system and these effects are mediated through the adrenal medulla and peripheral opioid receptors. The differential effects of κ opioid agonists on blood pressure and heart rate suggest that either the three κ agents interact differentially at the κ opioid receptors or the subtypes of receptors for the κ opioid exist.