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Selective modulation of receptor-mediated contraction in human coronary artery bypass conduits Experimental studies [1] suggest a selective role for membrane-bound calcium-independent phospholipase A2 (iPLA2β) in contributing to G-protein coupled receptor-mediated but not ion channel induced vaso-constriction in cerebral arteries and the abdominal aorta. We assessed whether this selective pathway may be present in human blood vascular conduits. We studied isolated internal mammary arteries (n = 6), obtained with written informed consent from patients undergoing coronary artery bypass grafting. The study was approved by the Local Research Ethics Committee. Receptor-mediated constrictor responses were assessed to phenylephrine (PE) at 80% of maximal concentration. We used S-bromoenolactone (S-BEL) as a probe of iPLA2β as S-BEL has been reported to be a suicide substrate inhibitor of the above enzyme. Results are for data+SEM. There was a significant increase in contraction during incubation of arteries with S-BEL 25uM in the presence of PE PE alone. After S-BEL washout there was a significant increase in contraction to KCl 60mM KCl alone. However, the post-S-BEL washout contractile response to PE was abolished PE post-S-BEL. A subsequent contractile response to further treatment with KCl 60mM [20.3±2.4 mN] returned to similar values to before S-BEL incubation. Our findings suggest that S-bromoenolactone has complex effects on contractile responses in the human internal mammary artery, with initial potentiation both of receptor-mediated and ion-channel mediated pathways, followed by selective abolition of receptor mediated constriction. Further work is needed to elucidate the diverse mechanisms responsible [2].
1.Park, KM, Trucillo, M, Serban, N, Cohen, RA, Bolotina, VM. Am J Physiol Heart Circ Physiol 2008;294:1183-1187.
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