Interaction of alpha- and beta-adrenergic receptor blocking agents: circulatory effects in the conscious rat

The alpha-receptor blockers phenoxybenzamine and phentolamine produced similar circulatory effects, e.g. hypotension and tachycardia in the conscious rat. The hypotension was more pronounced than that seen after an acute cervical transection of the spinal cord or after hexamethonium treatment. The tachycardia was blocked by drugs with beta 1-receptor blocking capacity while the hypotensive response was blocked by drugs with beta 2-receptor blocking capacity. The pronounced hypotension and tachycardia was absent after spinal transection, hexamethonium pretreatment or adrenal demedullation. In adrenal demedullated rats substitution with adrenaline after alpha-receptor blockade produced tachycardia and hypotension of the same degree as seen in intact rats after alpha-receptor blockade. There was no correlation between the degree of beta-blocker induced decrease in heart frequency and increase in blood pressure after alpha-receptor blockade, while a significant correlation was found between the alpha-blocker induced decrease in blood pressure and the subsequent beta 2-blocker induced increase in blood pressure. In spinal rats, pretreated with phentolamine, adrenaline caused a depressor response. This depressor response was converted into a pressor response by administration of beta-blockers at doses which seemed to correlate well with the doses of beta-blockers needed to effectively block the alpha-blocker induced hypotension in intact animals. It is concluded that acute administration of phentolamine or phenoxybenzamine, by blocking alpha-receptors causes a reflex increase in adrenaline output, which subsequently further decreases the blood pressure and increases the heart frequency by stimulation of beta-receptors.