Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm?
Endothelin-1 is an endothelium-derived vasoconstrictor peptide. Its circulating levels are below those known to evoke direct vascular effects. To study whether low concentrations of endothelin-1 potentiate the effects of other vasoconstrictor hormones, we suspended isolated human internal mammary and left anterior descending coronary artery rings in organ chambers for isometric tension recording. In mammary artery rings, the contractions to norepinephrine (3 x 10(-8) M) were potentiated by threshold (3 x 10(-10) M) and low concentrations (10(-9) M) of endothelin-1 (96 +/- 35% and 149 +/- 58% increase from control; p less than 0.01 and 0.001; n = 6). The inhibitor of endothelial nitric oxide formation L-NG-monomethyl arginine did not affect the potentiating effects of the peptide. The calcium antagonist darodipine (10(-7) M) prevented the potentiation of the response to norepinephrine evoked by endothelin-1. Similarly, contractions to serotonin (10(-7) or 3 x 10(-8) M) were amplified by endothelin-1 (3 x 10(-10) M) in the mammary (30 +/- 9%) and in the coronary arteries (59 +/- 25%). Endothelin-1 (10(-9) M) further potentiated the response (57 +/- 23% in mammary and 87 +/- 26% in coronary arteries; p less than 0.05; n = 7 and 3). The sensitivity of mammary arteries to calcium chloride was markedly enhanced in the presence of endothelin-1 (3 x 10(-10) M; concentration shift, eightfold; p less than 0.01; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, University Hospital, Basel, Switzerland.
Z H
ZH
Yang
V
V
Richard
L
L
von Segesser
E
E
Bauer
P
P
Stulz
M
M
Turina
T F
TF
Lüscher
D001158:Arteries / Q000187:drug effects*; D001696:Biomechanical Phenomena; D002118:Calcium / Q000494:pharmacology; D004056:Differential Threshold; D004357:Drug Synergism; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D009638:Norepinephrine / Q000494:pharmacology*; D009994:Osmolar Concentration; D010455:Peptides / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction
D016232:Endothelins; D010455:Peptides; D012701:Serotonin; D002118:Calcium; D009638:Norepinephrine