title: Serotonin-induced coronary spasm in a swine model. A minor role of defective endothelium-derived relaxing factor.
abstract: BACKGROUND
  Coronary spasm may be caused by endothelial dysfunction, vascular smooth muscle hyperreactivity, or both. We aimed to determine the relative role of endothelial dysfunction and vascular smooth muscle hyperreactivity in the pathogenesis of coronary artery spasm in the swine model in vivo.
  
  
  RESULTS
  In Göttingen miniature pigs given a high cholesterol diet, a segment of the left coronary artery was denuded and irradiated with x-ray (total, 30 Gy). Three months after endothelial denudation and irradiation, vasomotor responses of the denuded and control sites to agonists were assessed by quantitative arteriography. Serotonin (10 micrograms/kg) provoked coronary spasm at the denuded site (diameter reduction, 79 +/- 6%) associated with ST elevation but not at the nondenuded control site (21 +/- 6%). Intracoronary infusion of N omega-nitro-L-arginine methyl ester (LNNA, an inhibitor of endothelium-derived nitric oxide) of 1 and 3 mg/kg potentiated constriction evoked with serotonin (1, 3, 10 micrograms/kg) at the control site but did not alter it at the denuded site. However, serotonin-induced constriction after LNNA was still less at the control site (31 +/- 3%) than at the denuded site (80 +/- 5%). Endothelium-dependent vasodilation with substance P (0.1, 1, 10 ng/kg), which was inhibited by LNNA, was less (P < .01) at the denuded site than at the control site, whereas vasodilation with the nitrovasodilator SIN-1 (0.1, 1, 10 ng/kg) was comparable between the two sites. Histological study revealed regenerated endothelial cells and intimal thickening at the denuded site.
  
  
  CONCLUSIONS
  The results suggest that the denuded segment of the coronary artery with regenerated endothelium was associated with defective endothelium-dependent vasodilation mediated by nitric oxide and vascular smooth muscle hyperreactivity to serotonin. However, provocation of coronary spasm with serotonin resulted primarily from vascular smooth muscle hyperreactivity but not by defective nitric oxide production in this swine model.
authors.affiliation: Research Institute of Angiocardiography, Kyushu University School of Medicine, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fukai
authors.forename: K
authors.initials: K
authors.lastname: Egashira
authors.forename: H
authors.initials: H
authors.lastname: Hata
authors.forename: K
authors.initials: K
authors.lastname: Numaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Ohara
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Tomoike
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D017023:Coronary Angiography; D003329:Coronary Vasospasm / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D012701:Serotonin; D013373:Substance P / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature
chemical_list: D009569:Nitric Oxide; D012701:Serotonin; D013373:Substance P; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester