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Catecholamine-induced heart injury in mice: differential effects of isoproterenol and phenylephrine
Míriam Navarro-Sobrino1, Jordi Lorita, Maria Soley
1Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
Insights
Acute stress can injure the heart, but receptor roles are unclear. Alpha1-adrenergic receptors primarily cause catecholamine-induced heart injury, while beta-adrenergic receptors mediate beneficial effects.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Stress Response
Background:
- Catecholamines are involved in stress-induced heart injury.
- The specific roles of different adrenergic receptor types in this process are not fully understood.
Purpose of the Study:
- To investigate the contribution of alpha1- and beta-adrenergic receptors to catecholamine-induced heart injury and function.
- To compare the effects of phenylephrine (alpha1 agonist) and isoproterenol (beta agonist) on cardiac markers and tissue damage.
Main Methods:
- Comparison of plasma enzyme activities (LDH-1, AST) and cardiac lesion morphology in adrenaline-injected mice versus stressed mice.
- Langendorff-perfused rat heart experiments to assess adrenergic receptor contributions to heart rate and contractility.
- Administration of phenylephrine and isoproterenol to whole mice to evaluate their effects on cardiac markers and myocardial tissue.
Main Results:
- Phenylephrine, but not isoproterenol, increased cardiac enzyme activities (LDH-1, AST) in whole mice.
- Phenylephrine-injected hearts exhibited necrotic lesions and leukocyte infiltration, whereas isoproterenol-injected hearts showed fewer necrotic areas.
- Alpha1-adrenergic receptors played a minor role in the tonic effects of adrenaline on heart rate and contractility in perfused rat hearts.
Conclusions:
- The cardiotonic effects of catecholamines are mediated primarily by beta-adrenergic receptors.
- Acute catecholamine-induced heart injury is mainly mediated by alpha1-adrenergic receptors.
Abstract:
The involvement of catecholamines in stress-induced heart injury is well documented. However, the contribution of adrenergic receptor types is less understood. Both the profile of plasma marker enzyme activities (lactate dehydrogenase-1 and aspartate transaminase) and the distribution and morphology of the lesions observed in tissue sections of adrenaline-injected mice resembled those of stressed (restraint and cold exposed) mice. Next, we compared the effect of isoproterenol (beta-adrenergic agonist) and phenylephrine (alpha1-adrenergic agonist) on both heart function and tissue injury. In Langendorff-perfused rat hearts, alpha1-adrenergic receptors made a minor contribution to the tonic effect of adrenaline, as indicated by the lack of effect on the heart rate and the delayed negative inotropic effect of phenylephrine. However, in whole mice, phenylephrine but not isoproterenol, induced an increase of both lactate dehydrogenase-1 and aspartate transaminase activities. Hearts of phenylephrine-injected mice showed necrotic lesions in subendocardial areas of the left ventricle. In addition a scattered focal leukocyte infiltration around single apoptotic-like myocytes was observed in the ventricle wall. Hearts of isoproterenol-injected mice showed a similar number of apoptotic-like myocytes, but a much lower number of necrotic areas, than phenylephrine-injected animals. Our results suggest that the cardiotonic effect of catecholamines involves mainly the beta-adrenergic receptors. However, the acute catecholamine-induced heart injury involves mainly alpha1-adrenergic receptors.
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