Early decrease in secretin-, glucagon-, and isoproterenol-stimulated cardiac adenylate cyclase activity in rats...

Male Wistar albino rats received three times daily for one to five days 0.25 to 5.0 mg/kg D,L-isoproterenol intraperitoneally. D.L-Isoproterenol injections provoked a time dependent- and dose-related cardiac hypertrophy. With moderate hypertrophy, a selective decrease in secretin-stimulated adenylate cyclase activity occurred. When heart hypertrophy was more pronounced, greater losses in secretin-, as well as in D,L-isoproterenol-, glucagon-, guanine nucleotide-, and fluoride-stimulated enzyme activity developed. Hormone stimulations of adenylate cyclase were more severely, curtailed (60 to 65%) than guanine nucleotide or fluoride stimulations (40 to 45%). The accompanying loss in beta-receptors (35%) was proportionately lower than the loss of D,L-isoproterenol sensitivity of adenylate cyclase. This complex pattern of adenylate cyclase desensitization in heart membranes from animals chronically treated with D,L-isoproterenol is reminiscent of that observed in heart membranes from spontaneously hypertensive rats.