Cardiac beta-adrenoceptor desensitization after sinoaortic baroreceptors denervation or isoproterenol-pretreatment

The chronotropic reactivity to beta-adrenergic stimulation was studied in isolated perfused hearts from sinoaortic baroreceptors denervated (SAD) rats in the phases of maximal tachycardia (5 h) and normalized heart rate (15 days) or after repeated injection of isoproterenol (1 mg/kg, 3 times daily for 10 days). The threshold doses of isoproterenol needed to cause a significant acceleration of heart rate were significantly higher in acute SAD (1.6 X 10(-7)M), chronic SAD (3.2 X 10(-7)M), and isoproterenol-pretreated (6.4 X 10(-7)M) rats than in control rats (0.8 X 10(-7)M). The maximal increment in basal heart rate was lower in acute (59%) and chronic (48%) SAD rats and in isoproterenol-pretreated rats (26%) than in control rats (78%). These results suggest that the increased efferent sympathetic outflow to the heart induced by SAD causes desensitization of cardiac beta-adrenoceptors and may explain the gradual tachycardia disappearance in this SAD hypertensive rats.