T he a - adrenoceptor profile in human skeletal muscle resistance 1 arteries in critical limb ischaemia

Objective: We recently reported the hyper-responsiveness of human skeletal muscle resistance arteries (SkMRAs) to noradrenaline in critical limb ischaemia (CLI). In this study we investigated the characteristics of a -adrenoceptor subtypes and evaluated the agonist 1 affinity and adrenoceptor reserve in the ischaemic arteries. Methods: Human SkMRAs were isolated from non-ischaemic and ischaemic areas of limbs amputated for CLI. Subcutaneous resistance arteries were isolated from inguinal biopsies from healthy subjects. Arterial segments were mounted on a small vessel wire myograph. Results: Contractile responses to agonists, adrenaline and A-61603 (a -selective) were significantly increased in ischaemic arteries compared to those in non-ischaemic arteries. Receptor inactivation 1A studies indicated an increase in the a-adrenoceptor reserve in the ischaemic arteries but the affinity of noradrenaline was unaffected. Healthy subcutaneous arteries had a similar noradrenaline affinity but a higher receptor reserve than skeletal muscle arteries. In the ischaemic arteries, the antagonists prazosin (a -selective), 5-methyl-urapidil (a -selective) and BMY 7378 (a -selective) produced 1 1A 1D rightward shifts in the concentration response curves (CRCs) of noradrenaline giving pK s of 9.660.3, 8.460.2 and 7.160.4, B respectively. Pretreatment with 10 mM chloroethylclonidine decreased the contractile responses to noradrenaline and A-61603 to 5767 and 7264% of their respective controls. Conclusions: These results demonstrate that the ischaemic SkMRAs have an increased a-adrenoceptor reserve with no change in the predominant a -adrenoceptor profile. 1A  2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.