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 skeletal muscle resistance arteries to noradrenaline in patients with critical limb ischemia. We investigated whether this increased sensitivity in skeletal muscle resistance arteries is due to either alpha (1)- or alpha (2)-adrenoceptor-mediated responses or both. Methods: Skeletal muscle resistance arteries were isolated from the proximal (nonischemic) and distal (ischemic) parts of limbs amputated for critical limb ischemia and mounted on a small vessel 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 RS79948. 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 noradrenaline were not affected. Prazosin reduced the maximum responses to brimonidine, shifted the concentration response curves of noradrenaline and phenylephrine rightwards giving pK(B) values of 9.86 and 9.33, respectively. Maximum responses produced by all three agonists in distal vessels were significantly higher than those obtained in proximal vessels. Conclusions: Noradrenaline contractile responses in skeletal muscle resistance arteries are predominantly mediated by alpha (1)-adrenoceptors. Both alpha (1)- and alpha (2)-adrenoceptor-mediated responses are increased in the arteries from ischemic regions that may aggravate the decreased Mood flow to the limbs due to arterial occlusion. (C) 2001 Elsevier Science B.V. All rights reserved.