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Cardiovascular Research 2003 57(2):554-562; doi:10.1016/S0008-6363(02)00669-7
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

The {alpha}1-adrenoceptor profile in human skeletal muscle resistance arteries in critical limb ischaemia

Yagna P.R Jarajapua,*, John C McGrathb, Chris Hilliera and Allan MacDonalda

aVascular Assessment Unit, School of Biological and Biomedical Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA, UK
bAutonomic Physiology Unit, Institute of Biomedical and Life Sciences, Glasgow University, Glasgow, UK

* Corresponding author. Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, 1600 SW Archer Road, PO Box 100267, Gainesville, FL 32610-0267, USA. Tel.: +1-352-392-5317; fax: +1-352-392-9696. jarajapu{at}college.med.ufl.edu

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 {alpha}1-adrenoceptor subtypes and evaluated the agonist 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 ({alpha}1A-selective) were significantly increased in ischaemic arteries compared to those in non-ischaemic arteries. Receptor inactivation studies indicated an increase in the {alpha}-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 ({alpha}1-selective), 5-methyl-urapidil ({alpha}1A-selective) and BMY 7378 ({alpha}1D-selective) produced rightward shifts in the concentration response curves (CRCs) of noradrenaline giving pKBs of 9.6±0.3, 8.4±0.2 and 7.1±0.4, respectively. Pretreatment with 10 µM chloroethylclonidine decreased the contractile responses to noradrenaline and A-61603 to 57±7 and 72±4% of their respective controls. Conclusions: These results demonstrate that the ischaemic SkMRAs have an increased {alpha}-adrenoceptor reserve with no change in the predominant {alpha}1A-adrenoceptor profile.

KEYWORDS Adrenergic (ant)agonists; Arteries; Ischemia; Receptors; Vasoconstriction/dilation


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