α1- Adrenoceptors in Small Blood Vessels

The relative importance of the different α1-adrenoceptor subtypes in regulation of peripheral resistance and systemic arterial blood pressure is not clear, as the contribution of different subtypes to vasoconstriction varies with species and resistance vascular bed [1,2]. A further factor which may influence the subtypes involved in vasoconstriction physiologically is the manner of receptor activation, i.e., whether by circulating catecholamine or by neurally-released noradrenaline. Previous studies on adrenoceptors have suggested a topological difference between postsynaptic α1-adrenoceptor subtypes and sympathetic nerves. The observations with exogenous α1-adrenoceptor agonists and nerve-released noradrenaline over recent years have produced contrasting results. Studies on rat mesenteric small artery using exogenous agonists have revealed the role of α1A[3,4] or α1Bor α1L-adrenoceptors. In contrast nerve-evoked contractions in rat mesenteric small arteries were predominantly mediated by α1A-adrenoceptors [3,4]. Studies in mouse mesenteric small arteries have revealed a predominance of α1A-adrenoceptors in vasoconstriction to phenylephrine [5] and nerve-evoked contractions were mediated by α1B-adrenoceptors [6]. Honner and Docherty [7] have shown that responses of rat vas deferens to exogenous noradrenaline involve α1A-adrenoceptors while responses to nerve stimulation involve non-α1A-adrenoceptors, resembling the α1Dadrenoceptor. Yang and Chiba [8] have recently shown that in canine splenic artery exogenous noradrenaline produces contraction via α1A-adrenoceptors while noradrenaline released by nerve stimulation produced contraction via α1Band α1Dadrenoceptors. This may suggest that circulating catecholamine produce vasoconstriction via extrajunctional α1A-adrenoceptors while sympathetic nerve stimulation produces vasoconstriction via junction α1Band α1Dadrenoceptors in this artery. In vivo studies in pithed rats have shown pressor responses to electrical field stimulations were primarily mediated by α1A-adrenoceptors [9]. In contrast with sympathetic nerve-mediated stimulation, the pressor response curve for the α1adrenoceptor agonist cirazoline was competitively antagonised by both 5-methyl-urapidil and chloroethylclonidine in pithed rats, indicating a contribution from both α1Aand α1B-adrenoceptors [10]. In contrast to the above mentioned studies, other studies have shown no difference in the receptor subtype involved in responses to exogenous and neurally-released noradrenaline [4]. Therefore the