Mechanisms of alterations in cardiac membrane Ca2+ transport due to excess catecholamines.
The occurrence of excessive catecholamine release is often associated with stress due to the lifestyle of Western societies. Contrary to the general thinking that excess catecholamines produce cardiotoxicity mainly via binding to adrenoceptors, there is increasing evidence that catecholamine-induced deleterious actions may also occur through oxidative mechanisms. In this overview it is shown that a high dose of isoproterenol induces a biphasic change in cardiac Ca2+ transport in the sarcolemma and in sarcoplasmic reticulum. Both sarcolemmal and sarcoplasmic reticular Ca2+-transport activities are initially increased to maintain Ca2+ homeostasis and then are impaired, which may be associated with the occurrence of intracellular Ca2+ overload. On the other hand, mitochondrial Ca2+-transport activities exhibited a delayed increase. Pretreatment with vitamin E partially prevented the deleterious changes in cardiac membranes as well as the depressed energetic status of the heart muscle cell. It is concluded that excess catecholamines affect Ca2+-transport mechanisms primarily via oxidation reactions involving free radical-mediated damage. Thus drug approaches that reduce circulating catecholamines and/or prevent their oxidation should prove beneficial. A combination therapy involving inhibitors of catecholamine release, blockers of adrenoceptors, and antioxidants may be indicated for stress-induced heart disease.
Dhalla
K S
KS
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Rupp
H
H
Beamish
R E
RE
Dhalla
N S
NS
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D007545:Isoproterenol; D002118:Calcium