Role of ?2-adrenoceptor blockade and circulating adrenaline level for the pressor responses to ?-adrenoceptor blocking drugs in rats

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Abstract
The present experiments were designed to elucidate what mechanism(s) would be responsible for β-adrenoceptor blocking drugs (β-blockers)-induced pressor responses in rats. In urethane-anaesthetized rats, 6 β-blockers at i.v. doses ranging from 0.3 to 300 μg/kg evoked the pressor response in a dose-dependent manner. The relative potency in causing the pressor action was correlated not to their β1-blocking activities (r=0.374, P>0.05) but to their β2-blocking ones (r=0.856, P2-stimulation than noradrenaline, the dose difference for causing the diastolic blood pressure decrease by a 25 mm Hg being almost 80 times. In pithed rats, infusion of adrenaline at the rate of 0.02 μg/min caused a significant increase in plasma adrenaline level from 0.02±0.01 to 0.45±0.048 ng/ml, being close to basal level obtained in urethane-anaesthetized rats. Under this situation, propranolol (1–100 μg/kg i.v.) showed a distinct pressor response in a dose-dependent fashion as observed in adrenal intact rats anaesthetized with urethane. These results strongly suggest that the pressor responses to β-blockers are largely due to both their inhibitory actions on the vasodilatory β2-adrenoceptors and to their potentiating actions on the vascular response to circulating adrenaline.