[Effect of NG-nitro-L-arginine methylester on the secretion of endothelin-1 in vivo and in cultured endothelial cells].

We investigated the effect of nitric oxide, derived 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 (mPAP), pulmonary vascular resistance (PVR) and plasma endothelin-1 level of the femoral artery during hypoxic ventilation (FIO2 = 0.10) were 3.3 +/- 0.4kPa, 68.7 +/- 10.2kPa.s-1/L and 47.2 +/- 17.4ng/L respectively. NG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased the peak value of mPAP and PVR during hypoxic ventilation to 4.9 +/- 0.6 kPa and 160.9 +/- 34.6kPa. s/L and its effect lasted for 3 hours. Meanwhile, plasma endothelin-1 level in the femoral artery was increased to 68.2 +/- 20.6, 72.8 +/- 20.9, 75.8 +/- 22.7 ng/L at 60, 120, 180 minutes respectively after the injection of L-NAME (P < 0.05 vs hypoxic control before the injection). In cultured endothelial cells from human umbilical veins, endothelin-1 level of culture medium increased significantly in 10(-11) and 10(-7) mol/L L-NAME group (n = 9, P < 0.05 vs control group). 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.