Increased alpha(1)- and alpha(2)-adrenoceptor-mediated contractile responses of human skeletal muscle resistance arteries in chronic limb ischemia

Objective: Recently, we have shown augmented contractile responses of skele tal muscle resistance arteries to noradrenaline in patients with critical l imb ischemia. We investigated whether this increased sensitivity in skeleta l muscle resistance arteries is due to either alpha (1)- or alpha (2)-adren oceptor-mediated responses or both. Methods: Skeletal muscle resistance art eries were isolated from the proximal (nonischemic) and distal (ischemic) p arts of limbs amputated for critical limb ischemia and mounted on a small v essel wire myograph. Cumulative concentration response curves of the vessel segments to noradrenaline, phenylephrine and brimonidine were obtained in the presence or the absence of the selective antagonists, prazosin and RS79 948. Results: Noradrenaline and phenylephrine produced almost equal maximal contractile responses. Brimonidine responses were smaller and were almost abolished by 0.1 muM RS 79948 while those of phenylephrine and noradrenalin e were not affected. Prazosin reduced the maximum responses to brimonidine, shifted the concentration response curves of noradrenaline and phenylephri ne rightwards giving pK(B) values of 9.86 and 9.33, respectively. Maximum r esponses produced by all three agonists in distal vessels were significantl y higher than those obtained in proximal vessels. Conclusions: Noradrenalin e contractile responses in skeletal muscle resistance arteries are predomin antly mediated by alpha (1)-adrenoceptors. Both alpha (1)- and alpha (2)-ad renoceptor-mediated responses are increased in the arteries from ischemic r egions that may aggravate the decreased Mood flow to the limbs due to arter ial occlusion. (C) 2001 Elsevier Science B.V. All rights reserved.