title: Increased alpha(1)- and alpha(2)-adrenoceptor-mediated contractile responses of human skeletal muscle resistance arteries in chronic limb ischemia.
abstract: 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 (non-ischemic) 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 microM 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 blood flow to the limbs due to arterial occlusion.
authors: Vascular Assessment Group, School of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, G4 0BA, Glasgow, UK.
authors: Y P
authors: YP
authors: Jarajapu
authors: P
authors: P
authors: Coats
authors: J C
authors: JC
authors: McGrath
authors: A
authors: A
authors: MacDonald
authors: C
authors: C
authors: Hillier
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology; D001158:Arteries / Q000503:physiopathology; D000068438:Brimonidine Tartrate; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology*; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply*; D009638:Norepinephrine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D014662:Vasoconstrictor Agents; D000068438:Brimonidine Tartrate; D009638:Norepinephrine