Catecholamine-induced heart injury in mice: differential effects of isoproterenol and phenylephrine.
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.
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
Míriam
M
Navarro-Sobrino
Jordi
J
Lorita
Maria
M
Soley
Ignasi
I
Ramírez
D000316:Adrenergic alpha-Agonists / Q000633:toxicity; D000318:Adrenergic beta-Agonists / Q000633:toxicity; D000818:Animals; D002316:Cardiotonic Agents / Q000633:toxicity; D002395:Catecholamines / Q000633:toxicity*; D004837:Epinephrine / Q000633:toxicity; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006335:Heart Injuries / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D051379:Mice; D009206:Myocardium / Q000473:pathology; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D002395:Catecholamines; D010656:Phenylephrine; D007545:Isoproterenol; D004837:Epinephrine