LOCALIZATION OF ENDOTHELIN IMMUNOREACTIVITY AND DEMONSTRATION OF CONSTRICTORY ENDOTHELIN-A RECEPTORS IN HUMAN CORONARY-ARTERIES AND VEINS

Strong immunoreactivity for endothelins (ETs) was observed in the endo thelium of both human epicardial coronary arteries and veins. The cont ractile responses to ET-1, ET-2, and ET-3 were investigated in isolate d circular human coronary vessel segments. ET-1, ET-2, and ET-3 induce d significantly higher maximum contraction (measured in percentage of contraction induced by 60 mM potassium) and more potent responses in v eins as compared with arteries. ET-1 as compared with ET-2 induced equ al maximum contraction and equipotent responses both when tested in ar teries and veins, whereas ET-3 induced lower maximum contraction and l ess potent responses in both vessel types. FR 139317, a selective ET(A ) receptor antagonist, significantly decreased the potency of ET-1 and ET-2 responses in both human coronary arteries and veins, but the max imum effect obtained did not change significantly. The existence of ET immunoreactivity (IR) in endothelial cells from both human coronary a rteries and veins indicates that ETs may be released endogenously. The effect of the selective ET(A) receptor antagonist FR 139317 indicates that the contraction induced by ET-1 and ET-2 in both arteries and ve ins is mediated by ET(A) receptors.