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Evidence for involvement of catecholamines in the effect of morphine on ventricular automaticity in the rat
M Romero1, M L Laorden, J Hernandez
1Department of Pharmacology, Medical School of Sevilla, Spain.
Abstract:
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.
Insights
Morphine increases ventricular rate in injured rat hearts, an effect not blocked by naloxone, suggesting it doesn't act on opioid receptors. This action may involve presynaptic catecholamine release.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
Background:
- Ectopic automaticity in the heart can lead to arrhythmias.
- Opioid receptors are primarily known for their role in pain modulation.
Purpose of the Study:
- To investigate the effects of morphine on experimentally induced ectopic automaticity in rat ventricular tissue.
- To determine the potential involvement of opioid receptors and adrenergic mechanisms in morphine's cardiac effects.
Main Methods:
- Isolated rat right ventricle preparations were used to study ectopic automaticity.
- Concentration-response curves for morphine were generated in the presence and absence of naloxone.
- Experiments were also conducted in the presence of propranolol and in reserpinized rats.
Main Results:
- Morphine significantly increased ventricular rate, an effect not antagonized by naloxone, indicating a lack of postsynaptic opioid receptor involvement.
- High concentrations of naloxone alone decreased ventricular automaticity.
- Morphine's excitatory effect was abolished by propranolol and diminished in reserpinized rats, suggesting a presynaptic adrenergic mechanism.
Conclusions:
- Morphine's pro-arrhythmic effect on injured rat ventricles is likely mediated by indirect mechanisms, possibly involving presynaptic release of catecholamines.
- The findings suggest that morphine's cardiac effects are not primarily mediated through classical postsynaptic opioid receptors.