Analysis of the alpha-adrenoceptor-mediated, and other, components in the sympathetic vasopressor responses of the pithed rat

Abstract

The vascular receptors activated following sympatho-adrenal stimulation were determined by analysing the effects of 'selective' antagonists on the vasopressor response to spinal sympathetic nerve activation in the pithed rat. The net vascular response to adrenal stimulation was a balance between alpha-adrenoceptor-mediated vasoconstriction and beta-adrenoceptor-mediated vasodepression. Part of the alpha-adrenoceptor-mediated response was 'prazosin-sensitive' (alpha 1) and the remainder was abolished by rauwolscine (alpha 2). As with adrenal stimulation, direct sympathetic nerve stimulation of the vasculature evoked pressor responses which were partly resistant to prazosin. Rauwolscine only partly blocked the prazosin-sensitive component. Reserpine pretreatment led to smaller responses than prazosin plus rauwolscine. Thus, the response resistant to alpha-adrenoceptor antagonists could be mediated, in part, by adrenoceptors distinct from alpha-adrenoceptors, as currently defined. alpha, beta-Methylene ATP reduced the nerve-mediated pressor response after alpha-adrenoceptor blockade or reserpine pretreatment but not in drug-free controls. The results suggest that stimulation of the adrenal medulla can produce a vasopressor response which consists of summating alpha 1- and alpha 2-adrenoceptor-mediated components, and is identical to the effect of injected adrenaline. In contrast, the response to vasopressor nerve stimulation appears to be essentially mediated by alpha 1-adrenoceptors, with a facilitatory influence from alpha 2-adrenoceptors. A further response obtained after alpha-adrenoceptor blockade may contain a purinergic component and another which is adrenergic but not mediated by stimulation of alpha-adrenoceptors.