Attenuation of beta-adrenergic cardiac responses in chronically hypoxic rats with right ventricular hypertrophy

Rats were kept for 30 days in an O2-N2-mixture of gradually reduced O2 (18 leads to 6 Vol%) and constant CO2 (0.5 Vol percent). This induces a selective hypertrophy of the right ventricle and the ratio ventricular/body weight (g/kg) increased from 0.6 to 1.4 while it remained constant in the left heart. In the right and left ventricles of control animals the contents of myocardial ATP (4.0 muM/g) and of phosphocreatine (CP) (5.8 muM/g) were the same. These values were not significantly changed by hypertrophy. In the control animals, a single test-dose of isoproterenol (30 mg/kg), subcutaneously administered 2 hr before the heart was removed, caused a diminution of the ATP-content by 15 percent in the right ventricle and by 40 percent in the left. The CP-content was reduced by 40 percent on the right and by 50 percent on the left side. In the hypertrophied right ventricle, however, there was no major decrease in ATP and CP following the isoproterenol injection. In the nonhypertrophied left heart the response to isoproterenol was still detectable but much less than normal. As the chronotropic and hypotensive effects of isoproterenol were also lessened in the hypoxic animals it is concluded that a general reduction in the responsiveness to beta-adrenergic stimulation has occurred.