Stimulatory guanine nucleotide-binding protein and adenylate cyclase activities in Bio 14.6 cardiomyopathic hamsters at the hypertrophic stage

Abstract

The Bio 14.6 cardiomyopathic Syrian hamster is an animal model of human idiopathic cardiomyopathy. The pathogenesis of the disease in this animal has not yet been clearly elucidated. It is well known that α- and β-adrenergic receptors are increased in the myocardium of this animal, but that isoprenaline does not produce an augmented response. We examined the activity of cardiac stimulatory GTP-binding protein (Gs), which couple with β-adrenergic receptors to stimulate adenylate cyclase, in Bio 14.6 cardiomyopathic hamsters at 90 and 160 days of age. The cardiac norepinephrine concentration was significantly increased in Bio 14.6 hamsters compared with control hamsters (F1B) at 90 days of age (1,739±120 vs 1,470±161 ng/g wet tissue weight, p<0.05). Cardiac forskolin-stimulated adenylate cyclase activities at 90 and 160 days of age were lower in the cardiomyopathic hamsters than in the F1B controls (90 days old: 98±24 vs 122±29 pmol/min/mg protein, p<0.05; 160 days old: 74±13 vs 124±28 pmol/min/mg protein, p<0.01). Cardiac Gs activities at 90 and 160 days of age were significantly lower in Bio 14.6 hamsters than those in F1B hamsters (90 days old: 204±42 vs 259±49 pmol/min/mg protein, p<0.05; 160 days old: 156±39 vs 211±60 pmol/min/mg protein, p<0.05). We thus demonstrated functional defects in cardiac Gs protein and adenylate cyclase activity in the Bio 14.6 cardiomyopathic hamsters at 90 to 160 days of age (the hypertrophic stage of cardiomyopathy). Such defects could be one possible mechanism preventing an enhanced response to β-adrenergic stimulation in this animal and could also contribute to myocardial decompensation in the late stage of cardiomyopathy.