Age-related changes of in vivo beta-adrenergic responsiveness in normotensive and spontaneously hypertensive rats

The variations of plasma cyclic AMP concentration caused by propranolol and isoproterenol were studied in order to investigate endogenous stimulation and responsiveness of the beta-adrenoceptor-cyclic AMP system in vivo, in 7 and 18 week old unanaesthetized male SHR and WKY. In both age groups, the basal cyclic AMP level was higher in SHR than in controls but was significantly reduced to a comparable value in the two strains after intraperitoneal injection of 2.5 mg X kg-1 propranolol, a dose which markedly depressed or even abolished the effect of isoproterenol. Cumulative dose-response curves of plasma cyclic AMP concentration obtained in another group of rats after successive subcutaneous injections of isoproterenol showed that the ED50 value of this drug was higher in SHR than in WKY and increased in a parallel manner in the two strains between 7 and 18 weeks of age (respectively from 0.21 +/- 0.01 to 0.34 +/- 0.02 mumol X kg-1 in WKY and from 0.32 +/- 0.02 to 0.52 +/- 0.03 mumol X kg-1 in SHR). At the same time blood pressure increased much less markedly in WKY (from 115 +/- 4 to 119 +/- 2 mm Hg) than in SHR (from 134 +/- 3 to 179 +/- 3 mm Hg). Altogether these results show that endogenous beta-adrenergic stimulation of the cyclic AMP system was higher in SHR of both ages in spite of a diminished responsiveness of this system to exogenous isoproterenol.