Interaction between endothelin-1 and endothelium-derived relaxing factor in human arteries and veins.
Endothelin-1 is a 21-amino acid endothelial vasoconstrictor peptide that may be the physiological antagonist of endothelium-derived relaxing factor (EDRF). Endothelin-1 (10(-11)-3 x 10(-7) M) evoked potent contractions of isolated internal mammary arteries, internal mammary veins, and saphenous veins, which were enhanced in internal mammary veins as compared with internal mammary arteries (concentration shift, 6.3-fold; p less than 0.05) but not in the saphenous veins. Endothelial removal augmented the response to the peptide (at 3 x 10(-7) M) in internal mammary arteries (p less than 0.05) but not in veins. In the artery, EDRF released by acetylcholine or bradykinin reversed endothelin-1-induced contractions; in saphenous veins, both agonists were much less effective compared with the artery and veins contracted with norepinephrine (p less than 0.005-0.01). This inhibition of endothelium-dependent relaxations in veins occurred at half-maximal contractions but was most prominent at maximal contractions to the peptide. Nitric oxide similarly inhibited contractions to endothelin-1 and norepinephrine in internal mammary arteries, whereas in veins that were contracted with endothelin-1 but not with norepinephrine, the relaxations were blunted (p less than 0.005). The nitric oxide donor SIN-1 and sodium nitroprusside induced complete relaxations of internal mammary arteries but were less effective in veins contracted with endothelin-1 (p less than 0.005). Thus, in normal human arteries, EDRF inhibits endothelin-1-induced contractions, whereas the peptide specifically attenuates the effects of EDRF and nitrovasodilators in veins. This may be important in pathological conditions associated with increased levels of endothelin-1 and in veins used as coronary bypass grafts.
Lüscher
T F
TF
Department of Research, University Hospital, Basel, Switzerland.
Yang
Z
Z
Tschudi
M
M
von Segesser
L
L
Stulz
P
P
Boulanger
C
C
Siebenmann
R
R
Turina
M
M
Bühler
F R
FR
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D004347:Drug Interactions; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology*; D009574:Nitro Compounds / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology / Q000502:physiology*; D014661:Vasoconstriction; D014665:Vasodilator Agents / Q000494:pharmacology; D014680:Veins / Q000187:drug effects / Q000502:physiology
D016232:Endothelins; D009574:Nitro Compounds; D010455:Peptides; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000109:Acetylcholine; D001920:Bradykinin