IN-VITRO SUSCEPTIBILITY RHYTHMS - II - BIOLOGICAL-TIME-DEPENDENT DIFFERENCES IN EFFECT OF BETA(1)-ADRENERGIC AND BETA(2)-ADRENERGIC AGONISTS OF RAT AORTA AND INFLUENCE OF ENDOTHELIUM

Time-dependent variations in the vasodilator effects of beta-adrenergi c agonists terbutaline (Ter) and dobutamine (Dob) were studied in isol ated rings of rat thoracic aorta in both endothelium-intact and endoth elium-denuded preparations. Rats were housed in light from 08:00 to 20 :00 and in darkness from 20:00 to 08:00 and sacrificed at six differen t times of the day. In endothelium-intact and endothelium-denuded aort ic rings precontracted submaximally with phenylephrine (Phe), addition of Ter and Dob produced concentration-dependent relaxations. Removal of endothelium reduced the relaxant responses and area under curve (AU C) values and augmented the EC50 values to Ter and Dob at most, but no t all, time points. Two-way analysis of variance (ANOVA) revealed that AUCs, maximum responses, and EC50 values significantly depended on bo th treatment (endothelium intact/endothelium denuded) and time of sacr ifice. Results of the present study clearly show that in vitro sensiti vity of rat thoracic aorta to beta-adrenergic agonists displays tempor al variations depending on the time of animal sacrifice, and the prese nce of endothelium modifies the rhythmicity in beta-adrenergic activit y. These variations may be due to the circadian rhythmicity in the ade nylyl cyclase-cAMP-phosphodiesterase system that mediates the response s to beta-adrenergic agonists.