Interaction of α- and β-Adrenergic Receptor Blocking Agents: Circulatory Effects in the Conscious Rat

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Abstract
The α-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 fransection of the spinal cord or after hexamethonium treatment. The tachycardia was blocked by drugs with β-receptor blocking capacity while the hypotensive response was blocked by drugs with β2-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 α-receptor blockade produced tachycardia and hypotension of the same degree as seen in intact rats after α-receptor blockade. There was no correlation between the degree of β-blocker induced decrease in heart frequency and increase in blood pressure after α-receptor blockade, while a significant correlation was found between the α-blocker induced decrease in blood pressure and the subsequent β2-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 P-blockers at doses which seemed to correlate well with the doses of P-blockers needed to eFfectively block the a-blocker induced hypotension i n intact animals. It is concluded that acute administration of phentolamine or phenoxy-benzarnine, by blocking a-receptors causes a reflex increase i n adrenaline output, which subsequently further decreases the blood pressure and increases the heart frequency by stimulation of p-receptors.