Serotonin-induced coronary spasm in a swine model: A minor role of defective endothelium-derived relaxing factor

T. Fukai, K. Egashira, H. Hata, K. Numaguchi, Y. Ohara, T. Takahashi, H. Tomoike, A. Takeshita

Research output: Contribution to journalArticle

38 Scopus citations

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. Methods and Results. In Gottingen 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 μg/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(ω)-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 μg/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.

Original languageEnglish (US)
Pages (from-to)1922-1930
Number of pages9
JournalCirculation
Volume88
Issue number4 I
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

Keywords

  • atherosclerosis
  • endothelium
  • nitric oxide
  • substance P

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Fukai, T., Egashira, K., Hata, H., Numaguchi, K., Ohara, Y., Takahashi, T., Tomoike, H., & Takeshita, A. (1993). Serotonin-induced coronary spasm in a swine model: A minor role of defective endothelium-derived relaxing factor. Circulation, 88(4 I), 1922-1930. https://doi.org/10.1161/01.CIR.88.4.1922