STIMULATORY GUANINE-NUCLEOTIDE-BINDING PROTEIN IN FAILING HEART OF HAMSTERS AND RATS

The role of the stimulatory guanine nucleotide-binding protein (Gs) in heart failure is unclear. We therefore determined the amount of prote in and mRNA of Gs in the failing myocardium using two animal models: t he BIO 53.58 hamster, a model of genetic cardiomyopathy, and adriamyci n-treated rats (ADR rats), a model of secondary cardiomyopathy. The ma ximal number of myocardial beta-adrenoceptors in the BIO 53.58 hamster s as well as in the ADR rats was significantly lower than that in the respective controls, indicating that the beta-adrenoceptors were down- regulated in heart failure. Analysis by Western blot and Northern blot revealed a significant decrease in Gs protein and mRNA in the BIO 53. 58 hamsters relative to the control. There were no differences in the level of Gs protein or mRNA in the ADR rats vs the controls. The funct ional activity of Gs was investigated by measuring adenylate cyclase a ctivity. The activity of adenylate cyclase in response to stimulation by sodium fluoride or forskolin was decreased in the BIO 53.58 hamster s relative to control animals, whereas no differences were observed in the ADR rats vs the controls. Thus, alterations in Gs in the failing heart appear to differ according to its cause.