Inhibition of nitric oxide synthesis increases the secretion of endothelin-1 in vivo and in cultured endothelial cells.
The aim of this study is to investigate the effects of nitric oxide, formed from L-arginine, on the production of endothelin-1 in vivo and in cultured endothelial cells. In mechanically ventilated anesthetized dogs (n = 5), mean pulmonary arterial pressure (PAPm) and pulmonary vascular resistance (PVR) during hypoxic ventilation (FIO2 = 0.10) was 25 +/- 3.1 kPa and 68.7 +/- 10.2 kPa.s/L respectively. NG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased the peak value of PAPm and PVR during hypoxic ventilation to 36.6 +/- 4.7 kPa and 158.4 +/- 25 kPa.s/L and its effect lasted for 2-3 hours. Meanwhile, plasma endothelin-1 level in the femoral artery increased by 20.9 +/- 7.1, 25.6 +/- 7.7, 28.6 +/- 7.9 pg/ml at the 60th, 120th, 180th minute after the injection of L-NAME respectively (P < 0.05 vs hypoxic control before the injection). In cultured endothelial cells from umbilical veins, endothelin-1 level of culture medium in control group was 35.1 +/- 5.9 pg/10(5) cells/ml (n = 9). L-NAME increased endothelin-1 level to 42.8 +/- 4.9pg/10(5) cells/ml (n = 9, P < 0.05) in case of 10(-11) mol/L and to 43.0 +/- 4.7 pg/10(5) cells/ml in case of 10(-7) mol/L (n = 9, P < 0.05). These findings indicate that endogenous nitric oxide is an inhibitory modulator of hypoxic pulmonary vasoconstriction and that nitric oxide inhibits the production of endothelin-1 in vivo and in cultured vascular endothelial cells.
Cao
W B
WB
Department of Respiratory Medicine, PUMC Hospital, Beijing.
Zeng
Z P
ZP
Zhu
Y J
YJ
Luo
W C
WC
Cai
B Q
BQ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D004285:Dogs; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011651:Pulmonary Artery / Q000502:physiology; D014471:Umbilical Veins / Q000166:cytology; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester