Catecholamines, calcium and cardiomyopathy.
The cardiomyopathic Syrian hamster has a genetically transmitted form of dilated cardiomyopathy and is an important paradigm of myocardial disease, particularly for studies addressing the earliest stages of myocardial dysfunction. This model exhibits an increase in cardiac sympathetic tone in the presence of an altered expression of sarcolemmal calcium channels or of alpha 1 receptors, and a defective handling of calcium by both cardiomyocytes and vascular smooth muscle cells. Increased expression of the oncogene c-myc is evident in cardiomyocytes before any overt evidence of heart disease. Alterations in a nuclear phosphoprotein, which appears to be important in the regulation of gene expression, have also been identified. The disease becomes phenotypically manifest by the development of microvascular spasm, reperfusion injury and myocyte loss. Myocyte loss, in turn, burdens the remaining cells with an increasing load, increasing sympathetic stimulation, myocyte hypertrophy and further cell loss--a continuing vicious spiral that culminates in the development of myocardial failure. All of the features of hamster cardiomyopathy may be prevented by the administration of verapamil or prazosin to juvenile hamsters before the phenotypic onset of their heart disease. This understanding has led to the study of new imaging agents that promise the detection of such forms of cardiomyopathy in their earliest stages and a means by which the effects of therapy can be assessed. If such mechanisms are applicable to human cardiomyopathy, early treatment of patients with adrenergic antagonists or calcium antagonists should be beneficial.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D006224:Cricetinae; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012508:Sarcolemma / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism
D002395:Catecholamines; D002118:Calcium