[Endothelin-induced vasoconstriction in man: variable modification caused by endothelium-derived relaxing factor, Sodium nitroprusside and calcium antagonists].
The vascular effects of endothelin-1 (ET) were investigated in 25 healthy volunteers by measuring changes of forearm blood flow in response to brachial artery ET infusions. ET in a low dose (0.5 ng/min/100 ml tissue) resulted in a small but significant increase of forearm blood flow (FBF) from 2.3 +/- 1.5 to 2.5 +/- 1.5 ml/min/100 ml (n = 25, p less than 0.05) while higher dosages (25 and 50 ng/min/100 ml) resulted in significant decreases of FBF to 1.78 +/- 1.3 and 1.1 +/- 0.9 ml/min/100 ml (p less than 0.01). Neither sodium nitroprussid (n = 6) nor acetylcholine (n = 7) prevented ET-induced vasoconstriction. In contrast, both verapamil (n = 6) and nifedipine (n = 6) not only prevented ET-induced vasoconstriction but resulted in additional vasodilatation to values above those seen with the calcium antagonists alone. Thus, in human resistance vessels ET has a dual action with vasodilation occurring at low dosages and vasoconstriction at high dosages. Blockade of voltage-operated calcium channels prevents ET-induced vasoconstriction and unmasks the vasodilatory effects of high ET-dosages. Blockade of voltage-operated calcium channels but not cyclic GMP dependent vasodilation appears to be an effective tool in preventing ET-induced vasoconstriction.
Kiowski
W
W
Abteilung für Kardiologie, Universitätskliniken, Kantonsspital Basel.
Linder
L
L
Lüscher
T F
TF
Bühler
F R
FR
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D016232:Endothelins; D009599:Nitroprusside; D009569:Nitric Oxide; D014700:Verapamil; D009543:Nifedipine; D000109:Acetylcholine
Endothelin-induzierte Vasokonstriktion beim Menschen: Unterschiedliche Beeinflussung durch Endothelium-derived relaxing factor, Natrium-Nitroprussid und Calcium-Antagonisten.