Increased plasma level of endothelin-1 and coronary spasm induction in patients with vasospastic angina pectoris

Teruhiko Toyo-oka, Tadanori Aizawa, Nobuhiro Suzuki, Yasunobu Hirata, Takashi Miyauchi, Wee Soo Shin, Masashi Yanagisawa, Tomoh Masaki, Tsuneaki Sugimoto

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227 Scopus citations

Abstract

To elucidate the pathogenic contribution of a potent vasoconstrictor, endothelin-1, to coronary artery spasm, we provoked spasm with intracoronary administration of acetylcholine or ergonovine and performed sensitive immunoassays of plasma levels of endothelin-1 and atrial natriuretic factor (ANF) in the peripheral vein and coronary sinus of patients with a tentative diagnosis of vasospastic angina (VSA, n = 19). The validity of coronary sinus blood sampling was verified by simultaneous measurement of the ANF level. The plasma endothelin-1 levels in venous and coronary sinus blood of the spasm-provoked patients (n = 12) were 1.71-fold and 2.16-fold higher, respectively, than those of nonprovoked cases (n = 5, p<0.01). During left coronary spasm, the endothelin-1 level in coronary sinus transiently decreased from 2.27 ± 0.14 to 1.76 ± 0.14 pg/ml (p<0.01) and returned to the control level (1.98 ± 0.20 pg/ml) after the spasm resolved, whereas the change was equivocal during right coronary spasm. In contrast, the patients in whom spasm was not provoked showed no changes and maintained low endothelin-1 levels both before and after the maximal provocation (0.90 ± 0.13 versus 0.90 ± 0.13 pg /ml). These findings imply that 1) low but significant concentrations of immunoreactive endothelin-1 circulate in the human systemic and coronary vascular beds, 2) an increased plasma endothelin-1 level may predispose but might not be sufficient per se to induction of the coronary spasm, 3) some inhibitory mechanism to endothelin-1 secretion may occur into the coronary circulation during the spasm, or 4) VSA might be classified to two subtypes or substages-a type (or stage) with a high endothelin-1 level responding to the drug provocation and another type (or stage) with a low endothelin-1 level that is nonresponsive to the provocation.

Original languageEnglish (US)
Pages (from-to)476-483
Number of pages8
JournalCirculation
Volume83
Issue number2
DOIs
StatePublished - 1991

Keywords

  • atrial natriuretic factor
  • coronary circulation
  • endothelin-1
  • vasospastic angina

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Toyo-oka, T., Aizawa, T., Suzuki, N., Hirata, Y., Miyauchi, T., Shin, W. S., Yanagisawa, M., Masaki, T., & Sugimoto, T. (1991). Increased plasma level of endothelin-1 and coronary spasm induction in patients with vasospastic angina pectoris. Circulation, 83(2), 476-483. https://doi.org/10.1161/01.CIR.83.2.476