Endothelial vasodilator function is preserved at the spastic/inflammatory coronary lesions in pigs

Background-The question of whether or not endothelial vasodilator function in the spastic coronary artery is preserved is still controversial. We rece ntly developed a porcine model in which long-term and local treatment with interleukin-1 beta (IL-1 beta) from the adventitial site causes coronary ar teriosclerotic changes and vasospastic responses to autacoids. The aim of t his study was to examine the endothelial vasodilator function in our new po rcine model of the spasm both in vivo and in vitro. Methods and Results-A segment of the porcine coronary artery was asepticall y wrapped with cotton mesh that held absorbed IL-1 beta-bound microbeads. T wo weeks after the procedure, intracoronary administration of serotonin cau sed coronary vasospasm at the IL-1 beta-treated site (n = 10). Coronary vas odilatation to bradykinin, substance P, or an increase in coronary blood fl ow was preserved at the spastic site. Vasodilator responses to 3-morpholino sydnonimine (an NO donor) and nitroglycerin also were comparable between th e 2 sites. The vasoconstricting response to N-G-monomethyl-L-arginine and t he extent of the augmentation of the serotonin-induced vasoconstriction wer e comparable between the 2 sites. Organ chamber experiments showed that end othelium-dependent relaxations to bradykinin, the calcium ionophore A23187, and even the vasospastic agonist serotonin were: preserved at the spastic site, whereas contractions to serotonin were augmented at the spastic site regardless of the presence or absence of the endothelium (n = 6). Endotheli um-independent relaxations to sodium nitroprusside were also preserved at t he spastic site. Conclusions-These results indicate that endothelial vasodilator function is preserved at the spastic site and that the spasm is caused primarily by sm ooth muscle hypercontraction in our porcine model.