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Die Pharmazie - An International Journal Of Pharmaceutical Sciences
Wong, E;Li, J;Li, RR;Leung, G;
Objective: Although the α2-adrenoceptor receptor (α2-AR) agonist dexmedetomidine causes coronary vaso-constriction, activation of endothelial α2-ARs is known to induce vascular relaxation. Here, we used functional studies and molecular techniques to explore the involvement of different α2-AR subtypes (α2A-AR, α2B-AR α2C-AR) in the effects of dexmedetomidine on the coronary artery. Methods: After precontraction with prostaglandin F2a, changes in tension caused by dexmedetomidine, in the presence or absence of different antagonists, were studied in isolated right porcine coronary rings in organ chambers. The presence or absence of different subtypes of α2-ARs in right coronary arteries and in blocks of subendocardial myocardium containing coronary resistance arterioles was investigated using immunofluorescence, western blotting and reverse transcription-polymerase chain reaction (RT-PCR). Results: Dexmedetomidine caused relaxation of isolated large porcine coronary arteries, which was attenuated by rauwolscine (a non-selective α2-AR antagonist), BRL44408 (an α2A-AR antagonist) and ARC239 (an α2B-AR antagonist), and abolished by L-NAME (a nitric oxide synthase inhibitor) and pertussis toxin (a G iprotein inhibitor), and by removal of the endothelium. Although the relaxation could also be inhibited by MK912 (an α2C-AR antagonist), the pattern of inhibition suggested that it was due to a non-selective effect. The presence of α2A-AR in the endothelium of the right coronary artery, of α2B-AR in both the endothelium and vascular smooth muscle of the same artery, and of α2C-AR in the coronary resistance arterioles was confirmed by western blotting, RT-PCR and immunofluorescence. Conclusions : Expression of α2-AR subtypes is different in porcine coronary arteries of different sizes. Dexmedetomidine relaxes the large right coronary artery in an endothelium-dependent, α2A-AR, α2B-AR and nitric oxide-mediated manner. In contrast, α2C-AR is the only type of α2-AR in the resistance coronary arterioles and may be linked to vasoconstriction.