Liang-Xiong Fu

A new insight into adriamycin-induced cardiotoxicity

These clinical observations suggest that a biochemical mechanism more complex than direct redox cycling of adriamycin in the heart is likely to be involved in the pathogenesis of adriamycin cardiomyopathy [1]. The biochemical mechanism of adriamycin cardiotoxicity, however, remains a heated debate, although evidence is accumulating in support of several hypotheses. Adriamycin exposure may cause cellular damage via lipid peroxidation, interaction of adriamycin into nuclear and mitochondrial deoxyribonucleic acid, cellular calcium overloading, bioreductive activities leading to the formation of oxygen free radicals and alkylating species, and dysfunctions of mitochondria [2,3]

Decreased density of mesenteric arteries but not of myocardial endothelin receptors and function in rats with chronic ischemic heart failure.

Summary: Mesenteric artery and cardiac ventricular endothelin receptors and endothelin-1-induced pressor responses were studied in normal rats and rats with chronic congestive heart failure induced by myocardial ischemia (4 weeks after coronary artery ligation). In mesenteric arteries of rats with chronic ischemic heart failure, endothelin receptor density was significantly decreased by 59%, whereas the dissociation constant was increased 2.8-fold, as compared with controls. There were, however, no changes in endothelin-receptor density or the dissociation constant in cardiac ventricular membrane preparations from rats with congestive heart failure as compared with controls. In pithed rats with congestive heart failure there was a reduced pressor response to a bolus injection of endothelin-1 (800 pmole/kg body weight), while the vasodilatory response was unaltered as compared with sham-operated controls. These results demonstrate that there is a decreased vascular endothelin-receptor function due to a down-regulated endothelin receptor. The in vivo data indicate that this is due to impaired endothelin A but not endothelin B receptor function. Thus, there is an impaired arterial but not cardiac ventricular endothelin receptor-mediated signalling system in the rat with chronic ischemic heart failure.

An overview of beta-adrenoceptors and signal transduction — desensitization in cardiac disease and effect of beta-blockade

The beta-adrenoceptor-directed signal transduction system in myocardium has attracted wide attention since the activation or inhibition of this signal transduction by endogenous or therapeutically administered drugs has obvious and important clinical relevance to a wide range of human cardiac disease. A concise review will be given concerning the interactions of the components and desensitization of the beta-adrenoceptor-guanine nucleotide binding regulatory protein-adenylyl cyclase system, and effect of beta-blockade on myocardial beta-adrenoceptors and signal transduction