Lahera V, Salom M G, Miranda-Guardiola F, Moncada S, Romero J C
Department of Physiology, Mayo School of Medicine, Rochester, Minnesota 55905.
Am J Physiol. 1991 Dec;261(6 Pt 2):F1033-7. doi: 10.1152/ajprenal.1991.261.6.F1033.
The dose-dependent effects of intravenous infusions of nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.1, 1, 10, and 50 micrograms.kg-1.min-1), were studied in anesthetized rats to determine whether the inhibitory actions of L-NAME are manifested primarily in alterations of renal function or whether they are the consequences of the increase in systemic blood pressure. Mean arterial pressure (MAP) was not altered by the intravenous L-NAME infusions of 0.1 and 1.0 microgram.kg-1.min-1. However, 0.1 microgram.kg-1.min-1 L-NAME induced a 30% decrease in urine flow rate (UV). The administration of 1.0 microgram.kg-1.min-1 L-NAME, in addition to decreasing UV, also decreased urinary sodium excretion (UNaV) and renal plasma flow (RPF). The intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 produced significant increases in MAP that reversed the initial fall in UV and UNaV, despite decreasing RPF and glomerular filtration rate (GFR). The administration of L-arginine alone (10 micrograms.kg-1.min-1) did not modify any of the parameters measured, but it effectively prevented all the hemodynamic and renal changes induced by the infusion of 50 micrograms.kg-1.min-1 L-NAME. These results suggest that the decrease in nitric oxide production induced by the intravenous infusion of L-NAME affects renal excretion of sodium and water in the absence of any significant change in blood pressure. At larger doses, L-NAME also produces hypertension that overrides the initial antinatriuretic effect.
研究了静脉输注一氧化氮(NO)合成抑制剂NG-硝基-L-精氨酸甲酯(L-NAME;0.1、1、10和50微克·千克⁻¹·分钟⁻¹)的剂量依赖性效应,以确定L-NAME的抑制作用主要表现为肾功能改变,还是全身血压升高的结果。静脉输注0.1和1.0微克·千克⁻¹·分钟⁻¹的L-NAME未改变平均动脉压(MAP)。然而,0.1微克·千克⁻¹·分钟⁻¹的L-NAME使尿流率(UV)降低了30%。给予1.0微克·千克⁻¹·分钟⁻¹的L-NAME,除降低UV外,还降低了尿钠排泄(UNaV)和肾血浆流量(RPF)。静脉输注10.0和50.0微克·千克⁻¹·分钟⁻¹的L-NAME使MAP显著升高,尽管RPF和肾小球滤过率(GFR)降低,但逆转了UV和UNaV的初始下降。单独给予L-精氨酸(10微克·千克⁻¹·分钟⁻¹)未改变任何测量参数,但有效预防了输注50微克·千克⁻¹·分钟⁻¹的L-NAME引起的所有血流动力学和肾脏变化。这些结果表明,静脉输注L-NAME引起的一氧化氮生成减少在血压无任何显著变化的情况下影响钠和水的肾排泄。在较大剂量时,L-NAME还会产生高血压,从而掩盖最初的利钠作用。