Nonspecific supersensitivity induced by reserpine in guinea pig cardiac ventricle tissue

The depletion of norepinephrine stores by chronic reserpine pretreatment is thought to be responsible for the development of supersensitivity in cardiac tissue. The present study was designed to determine if reserpine-induced supersensitivity could be demonstrated in isolated guinea pig right ventricular strips, if it was associated with beta adrenoceptor proliferation and was specific for beta adrenoceptor agonists. In addition, reserpine dose-dependency of the phenomenon was tested for by using two pretreatment regimens to determine if supersensitivity was the result of direct or possibly toxic effects of reserpine. Pretreatment of guinea pigs with reserpine (0.1 mg/kg/day) for 7 days resulted in over 90% depletion of cardiac norepinephrine stores. Supersensitivity to the inotropic effects of isoproterenol, impromidine and forskolin was demonstrated. Associated with the supersensitivity was a significant increase in beta adrenoceptor density. Muscarinic receptor density was actually decreased. This pretreatment regimen also was associated with a significant (30%) drop in body weight suggesting that the phenomenon might be the result of a direct toxic effect of reserpine. Pretreatment of guinea pigs with a lower dose of reserpine (0.03 mg/kg/day) for 7 days produced the same degree of norepinephrine depletion, nonspecific inotropic supersensitivity and beta adrenoceptor proliferation in the absence of a significant reduction in body weight. The degree of supersensitivity induced by the two pretreatment regimens was between 2- to 3-fold for all three agonists tested.(ABSTRACT TRUNCATED AT 250 WORDS)