INCREASED PLASMA-LEVEL OF ENDOTHELIN-1 AND CORONARY SPASM INDUCTION IN PATIENTS WITH VASOSPASTIC ANGINA-PECTORIS

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.