The role of cyclic AMP in isoprenaline-induced cardiac necroses in the rat.

Abstract

Abstract Single administrations of isoprenaline chloride (6–36 μg/kg, s.c.) resulted in the appearance of acute myocardial necroses in the rat within 24 h. The percentage of animals with lesions was directly related to the dose of isoprenaline. Dibutyryl cyclic AMP (1–50 mg/kg, i.p.) induced myocardial lesions of the same type, however the percentage of animals affected was not dose-dependent. Pretreatment with theophylline (75 mg/kg, s.c.) administered to inhibit cardiac phosphodiesterase activity, induced a 48-fold reduction in the ED50 of isoprenaline and potentiated the nucleotide-induced cardiac lesions which became dose-dependent. Thus, a mediatory role for cyclic AMP in the isoprenaline-induced cardiac necroses in the rat is suggested.