Endothelin-1- and endothelin-3-induced vasorelaxation via common generation of endothelium-derived nitric oxide.
The vasorelaxant effects by endothelin-1 (ET-1) and endothelin-3 (ET-3), and their mechanisms of action were studied in isolated porcine pulmonary arterial strips. ET-1 and ET-3 dose-dependently (10(-9) - 10(-8) M) relaxed vascular strips precontracted with norepinephrine only in the presence of endothelium. The maximal vasorelaxant effect by ET-1 was about 70% of that by ET-3. The ET-1- and ET-3- induced vasorelaxation was blocked by NG-nitro-L-arginine, an inhibitor of nitric oxide synthesis, and methylene blue, an inhibitor of soluble guanylate cyclase. The present data suggest that vascular smooth muscle relaxation induced by ET-1 and ET-3 is mainly ascribed to synthesis and release of nitric oxide from L-arginine in endothelium.
Namiki
A
A
Third Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
Hirata
Y
Y
Ishikawa
M
M
Moroi
M
M
Aikawa
J
J
Machii
K
K
D000818:Animals; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D016232:Endothelins; D009569:Nitric Oxide; D009638:Norepinephrine