Deng Aihua, Miracle Cynthia M, Suarez Jorge M, Lortie Mark, Satriano Joseph, Thomson Scott C, Munger Karen A, Blantz Roland C
Division of Nephrology-Hypertension, University of California, San Diego, California 92161, USA.
Kidney Int. 2005 Aug;68(2):723-30. doi: 10.1111/j.1523-1755.2005.00450.x.
Oxygen mitochondrial effects consumption by the kidney (Qo(2)), is linearly related to sodium reabsorption (T(na)), but recent studies suggest this relationship is variable and that metabolic efficiency (Qo(2)/T(na)) in kidney is regulated by hormonal factors. In the dog, nonselective inhibitors of nitric oxide synthase (NOS) increase Qo(2) and Qo(2)/T(na). Glomerular hemodynamic and reabsorptive consequences of NOS inhibition require angiotensin II (Ang II), implying an antagonistic relationship between nitric oxide and Ang II. Effects of NOS inhibition in the rat, the role of Ang II and the responsible NOS isoform have not been elucidated.
Kidney blood flow [renal blood flow (RBF)], glomerular filtration rate (GFR), and Qo(2)/T(na) were measured before and during intravenous administration of N(G)-monomethyl-l-arginine (L-NMMA), a nonselective NOS inhibitor, in control and losartan (Ang II receptor blocker)-treated rats and rats administered S-methyl-L-thiocitrulline (SMTC), a NOS-1 inhibitor. Effects of SMTC on oxygen consumption were also examined in freshly harvested proximal tubules.
L-NMMA and high-dose SMTC decreased RBF, but L-NMMA + losartan and low-dose SMTC did not. Qo(2)/T(na) increased in both L-NMMA groups. Both low- and high-dose SMTC also increased Qo(2)/T(na). SMTC increased Qo(2) in proximal tubules in vitro at presumed lower levels of vectorial NaCl transport. Results suggest this effect was not mediated by influences on sodium transport alone.
Nonselective NOS inhibition increases the oxygen costs of kidney function independent of Ang II. Kidney NOS-1 is responsible for these in vivo and in vitro effects. In vitro observations suggest that NOS-1 acts in part via effects on basal metabolism and mitochondrial function.
肾脏的氧线粒体消耗率（Qo₂）与钠重吸收率（Tₙₐ）呈线性相关，但最近的研究表明这种关系是可变的，并且肾脏中的代谢效率（Qo₂/Tₙₐ）受激素因素调节。在犬类中，一氧化氮合酶（NOS）的非选择性抑制剂会增加Qo₂和Qo₂/Tₙₐ。NOS抑制对肾小球血流动力学和重吸收的影响需要血管紧张素II（Ang II）参与，这意味着一氧化氮和Ang II之间存在拮抗关系。NOS抑制在大鼠中的作用、Ang II的作用以及相关的NOS同工型尚未阐明。
在对照大鼠、氯沙坦（Ang II受体阻滞剂）处理的大鼠以及给予S-甲基-L-硫代瓜氨酸（SMTC，一种NOS-1抑制剂）的大鼠静脉注射非选择性NOS抑制剂N(G)-单甲基-L-精氨酸（L-NMMA）之前和期间，测量肾血流量[肾血流量（RBF）]、肾小球滤过率（GFR）和Qo₂/Tₙₐ。还在新鲜分离的近端小管中研究了SMTC对氧消耗的影响。
L-NMMA和高剂量SMTC降低了RBF，但L-NMMA +氯沙坦和低剂量SMTC没有。两个L-NMMA组的Qo₂/Tₙₐ均升高。低剂量和高剂量SMTC也都增加了Qo₂/Tₙₐ。在体外，假定载体NaCl转运水平较低时，SMTC增加了近端小管中的Qo₂。结果表明，这种作用并非仅由对钠转运的影响介导。
非选择性NOS抑制增加了肾功能的氧消耗成本，且与Ang II无关。肾脏NOS-1负责这些体内和体外效应。体外观察表明，NOS-1部分通过对基础代谢和线粒体功能的影响发挥作用。
