Functional characterization of alpha(1)-adrenoceptor subtypes in human skeletal muscle resistance arteries

1 alpha (1)-adrenoceptor subtypes in human skeletal muscle resistance arter ies were characterized using agonists noradrenaline (non-selective) and A61 603 (alpha (1A)-selective), the antagonists prazosin (non-selective), 5-met hyl-urapidil (alpha (1A)-selective) and BMY7378 (alpha (1D)-selective) and the alkylating agent chloroethylclonidine (Dreferential for alpha (1B)). 2 Small arteries were obtained from the non-ischaemic skeletal muscle of li mbs amputated for critical limb ischaemia and isometric tension recorded us ing wire myography. 3 Prazosin antagonized responses to noradrenaline with a pA(2) value of 9.1 8, consistent with the presence of alpha (1)-adrenoceptors, although the Sc hild slope (1.32) was significantly different from unity. 4 5-Methyl-urapidil competitively antagonized responses to noradrenaline wi th a pK(B) value of 8.48 and a Schild slope of 0.99, consistent with the pr esence of alpha (1A)-adrenoceptors. In the presence of 300 nM. 5-methyl-ura pidil, noradrenaline exhibited biphasic concentration response curves, indi cating the presence of a minor population of a 5-methyl-urapidil-resistant subtype. 5 Contractile responses to noradrenaline were not affected by 1 muM chloroe thylclonidine suggesting the absence of alpha (1B)-adrenoceptors. Maximum r esponses to noradrenaline and A61603 were reduced to a similar extent by 10 muM chloroethylclonidine, suggesting an effect of chloroethylcionidine at alpha (1A)-adrenoceptors at the higher concentration. 6 BMY7378 (10 and 100 nM) had no effect on responses to noradrenaline. BMY7 378 (1 muM) poorly shifted the potency of noradrenaline giving a pA(2) of 6 .52. These results rule out the presence of the alu-subtype. 7 These results show that contractile responses to noradrenaline in human s keletal muscle resistance arteries are predominantly mediated by the alpha (1A)-adrenoceptor subtype with a minor population of an unknown alpha (1)-a drenoceptor subtype.