Influence of neuronal uptake on the contribution of smooth muscle alpha 2-adrenoceptors to vasoconstrictor responses to noradrenaline in SHR and WKY isolated tail arteries.

Abstract

The effects of the selective alpha-adrenoceptor antagonists idazoxan (alpha 2) and prazosin (alpha 1) were examined on responses to exogenous noradrenaline and to sympathetic nerve stimulation in SHR and WKY rat isolated perfused proximal tail artery segments. The influence of inhibition of neuronal uptake with cocaine on the effects of these antagonists was also determined. The following results were obtained: Prazosin (10 nmol/l) was equieffective in antagonising responses to exogenous noradrenaline and sympathetic nerve stimulation in both SHR and WKY arteries and the degree of antagonism was similar in either the presence or the absence of neuronal uptake inhibition. In contrast to prazosin, the effects of idazoxan (100 nmol/l), on both exogenous noradrenaline and sympathetic nerve stimulation were dependent on the degree of inhibition of neuronal uptake. In SHR arteries, the degree of antagonism of responses to exogenous noradrenaline by idazoxan (100 nmol/l) decreased progressively as the concentration of cocaine was increased to 4 and 40 mumol/l; in WKY arteries, even in the absence of cocaine, idazoxan (100 nmol/l) did not antagonise responses to exogenous noradrenaline. In SHR arteries, the responses to sympathetic nerve stimulation were reduced to a lesser extent by idazoxan (100 nmol/l) when the concentration of cocaine was increased to 4 mumol/l than in the absence of cocaine. In WKY arteries, idazoxan (100 nmol/l) reduced the responses to sympathetic nerve stimulation in the absence of cocaine. However, this concentration of idazoxan increased the responses to nerve stimulation in the presence of cocaine. Our results indicate that smooth muscle alpha 2-adrenoceptors are present in SHR tail arteries, both intra- and extrajunctionally.(ABSTRACT TRUNCATED AT 250 WORDS)