The α1-adrenoceptor profile in human skeletal muscle resistance arteries in critical limb ischaemia

Jarajapu, Y. P. R., McGrath, J. C. , Hillier, C. and MacDonald, A. (2003) The α1-adrenoceptor profile in human skeletal muscle resistance arteries in critical limb ischaemia. Cardiovascular Research, 57, pp. 554-562. (doi: 10.1016/S0008-6363(02)00669-7) (PMID:12566128)

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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 α1-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 (α1A-selective) were significantly increased in ischaemic arteries compared to those in non-ischaemic arteries. Receptor inactivation studies indicated an increase in the α-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 (α1-selective), 5-methyl-urapidil (α1A-selective) and BMY 7378 (α1D-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 α-adrenoceptor reserve with no change in the predominant α1A-adrenoceptor profile.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McGrath, Professor John
Authors: Jarajapu, Y. P. R., McGrath, J. C., Hillier, C., and MacDonald, A.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Cardiovascular Research
Publisher:Oxford University Press
ISSN (Online):1755-3245
Published Online:01 February 2003

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