Evidence for involvement of catecholamines in the effect of morphine on ventricular automaticity in the rat.
1. The present study examined the effects of morphine on ectopic automaticity induced by local injury in the isolated right ventricle of the rat. 2. Morphine (10(-7)-5 x 10(-5) M) induced a significant increase of ventricular rate similar to that produced by noradrenaline. The excitatory effect of morphine was not modified by the presence of naloxone (5 x 10(-5) M). The maximal effect obtained with morphine in the presence of naloxone was 60 +/- 7%, similar to that obtained with morphine alone (67 +/- 15%). The EC50 values for morphine in the absence (0.89 x 10(-7) M) and presence of naloxone (0.87 x 10(-7) M) were also similar. Apparently this effect is not mediated by postsynaptic opioid receptors. 3. The ventricular automaticity induced in isolated right ventricle of the rat was significantly decreased by the highest concentrations of naloxone (5 x 10(-5) and 10(-7) M). 4. Morphine (10(-9)-5 x 10(-5) M) did not significantly change ventricular automaticity in the presence of propranolol (5 x 10(-8) M) or in reserpinized rats (5 mg kg-1 i.p. 24 h before the experiments). The maximal increases induced by morphine in the presence of propranolol or in reserpinized rats were 5 +/- 0.8% and 16 +/- 14.7% respectively. These results were significantly different from the maximal increase obtained without propranolol or with non-reserpinized animals. It is possible that the effects of morphine on ventricular automaticity could be mediated by an indirect effect located presynaptically at the adrenergic nerve terminals through the release of catecholamines.
Romero
M
M
Department of Pharmacology, Medical School of Sevilla, Spain.
Laorden
M L
ML
Hernandez
J
J
Serrano
J S
JS
D000818:Animals; D004347:Drug Interactions; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D016278:Ventricular Function, Right / Q000187:drug effects
D009270:Naloxone; D009020:Morphine; D012110:Reserpine; D011433:Propranolol; D009638:Norepinephrine