Different effects of endothelin-1 on cAMP- and cGMP-mediated vascular relaxation in human arteries and veins: comparison with norepinephrine.
Endothelin-1 (ET-1) is a new cardiovascular hormone produced by endothelial cells. The vascular effects of the peptide and its interaction with cAMP- and cGMP-dependent relaxation were investigated in human arteries and veins. Internal mammary arteries and veins and saphenous veins were obtained intraoperatively and suspended in organ chambers; isometric tension was recorded. The blood vessels were contracted with ET-1 or norepinephrine and relaxations to prostacyclin or sodium nitroprusside were studied. Mammary veins exhibited an enhanced sensitivity to ET-1 (10(-11) to 3 X 10(-7) M) as compared to the artery and saphenous vein (log shift at ED50: 32- and 79-fold, respectively; p less than 0.005). In saphenous veins maximally contracted with ET-1, relaxations to prostacyclin were blunted as compared to the artery (p less than 0.005; n = 5). Similarly, ET-1 inhibited relaxations to sodium nitroprusside in the vein, but not in the artery. In contrast, venous rings contracted with norepinephrine were more sensitive to sodium nitroprusside than the artery. Thus, the human mammary vein, but not the saphenous vein, is more sensitive to the vasoconstrictor effects of ET-1 when compared to the mammary artery. In veins, ET-1 but not norepinephrine inhibits the vascular effects of prostacyclin and sodium nitroprusside, suggesting a specific interaction of the peptide with cAMP- and cGMP-dependent relaxation.
Yang
Z H
ZH
Department of Research, University Hospitals, Basel, Switzerland.
Bühler
F R
FR
Diederich
D
D
Lüscher
T F
TF
D001158:Arteries / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D016232:Endothelins; D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D012501:Saphenous Vein / Q000187:drug effects; D014680:Veins / Q000187:drug effects
D016232:Endothelins; D010455:Peptides; D009599:Nitroprusside; D009569:Nitric Oxide; D000242:Cyclic AMP; D006152:Cyclic GMP; D009638:Norepinephrine