Efficiency of β-adrenoceptor subtype coupling to cardiac adenylyl cyclase in cardiomyopathic and control hamsters

Densities of β-adrenoceptor subtypes and their contributions to stimulation of adenylyl cyclase were studied in heart ventricles from cardiomyopathic (BIO 8262) and control Syrian hamsters (CLAC) at 4 different ages: 30, 100, 200 and 300 days. In BIO ventricles neither total β-adrenoceptor density nor that of the β₁-adrenoceptor subtype differed from the controls, whereas the density of β₂-adrenoceptors was significantly higher in myocardium from 200- and 300-day-old BIO compared to that from age-matched CLAC hamsters. Stimulation of adenylyl cyclase by the non-selective β-adrenoceptor agonist isoprenaline did not differ between strains, but the β₁-adrenoceptor mediated component was significantly reduced in cardiomyopathic hamsters of all age groups. In 300-day-old animals β₁-adrenoceptors accounted for 83% (CLAC) and 68% (BIO) of total β-adrenoceptor binding sites, whereas only 26% (CLAC) and 6% (BIO) of the isoprenaline effect on cAMP formation were mediated via β₁-adrenoceptors. Thus, the present study shows a lower coupling efficiency of β₁-adrenoceptors compared to the β₂-adrenoceptor subtype in ventricles from healthy Syrian hamsters and a progressive, further reduction in β₁-adrenergic function in cardiomyopathic animals.