Consequences of reduced production of NO on vascular reactivity of porcine coronary arteries after angioplasty: importance of EDHF

The consequences of the reduced production of nitric oxide (NO) by cells from regenerated endothelium were investigated by measuring membrane potential of smooth muscle cells (SMCs), isometric tension and cyclic nucleotides content in porcine coronary arteries with intimal thickening, four weeks following angioplasty. Under basal conditions, SMCs of coronary arteries with regenerated endothelium were depolarized by 10 mV. This depolarization was associated with 82% decreased level of cGMP without alteration in cAMP. Sodium nitroprusside (SNP, 1 μM) repolarized SMCs of the previously denuded coronary arteries. This repolarization was abolished by 1H‐[1,2,4]‐oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ, 10 μM) and not suppressed by glibenclamide (10 μM), iberiotoxin (IbTX, 100 nM) and the combination of charybdotoxin (ChTX, 40 nM) plus apamin (100 nM). Four‐aminopyridine (4‐AP, 1‐5 mM) generated spontaneous rhythmic activities only in coronary arteries with regenerated endothelium which were abolished by SNP. Nevertheless, 4‐AP did not suppress the repolarization induced by SNP. In vascular segments with regenerated endothelium, contracted with prostaglandin F2α (PGF2α), relaxation to bradykinin (BK, 30 nM) was unaltered despite a reduced production of cGMP (−70%). Indomethacin (10 μM) plus Nω‐nitro‐L‐arginine (L‐NA, 30 μM) reduced relaxation (−12% and −35% for native and regenerated endothelium, respectively) but did not abolish it. The hyperpolarizations induced by BK were not altered by the presence of indomethacin and L‐NA and were unchanged in segments with regenerated endothelium. These data are consistent with a contribution of impairment in NO production to the depolarization of SMCs. Nevertheless, EDHF responses to BK are sufficient to maintain a normal relaxation after angioplasty. British Journal of Pharmacology (2002) 136, 1153–1161. doi:10.1038/sj.bjp.0704828