Institute of Molecular Medicine, University of Southern Denmark, and Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.
Clin Sci (Lond). 2012 Jan;122(2):63-73. doi: 10.1042/CS20110144.
NO (nitric oxide) may be involved in fluid homoeostasis. We hypothesized that increases in NO synthesis contribute to acute, saline-induced natriuresis, which, therefore, should be blunted when NO availability is stabilized. Young men were studied during simultaneous infusions of L-NAME [NG-nitro-L-arginine methyl ester; bolus of 750 μg·kg⁻¹ of body weight and 8.3 μg·min⁻¹·kg⁻¹ of body weight] and SNP (sodium nitroprusside), the latter at a rate preventing L-NAME from increasing total peripheral resistance ('NO-clamping'). Slow volume expansion (saline, 20 μmol of NaCl·min⁻¹·kg⁻¹ of body weight for 3 h) was performed with and without concomitant NO-clamping. NO-clamping itself decreased RPF (renal plasma flow; P~0.02) and tended to decrease arterial blood pressure [MABP (mean arterial blood pressure)]. Volume expansion markedly decreased the plasma levels of renin, AngII (angiotensin II) and aldosterone (all P<0.001), while MABP (oscillometry), heart rate, cardiac output (impedance cardiography), RPF (by p-aminohippurate), GFR [glomerular filtration rate; by using 51Cr-labelled EDTA] and plasma [Na+] and [K+] remained constant. Volume expansion increased sodium excretion (P<0.02) at constant filtered load, but more so during NO-clamping than during control (+184% compared with 52%; P<0.0001). Urinary nitrate/nitrite excretion increased during volume expansion; plasma cGMP and plasma vasopressin were unchanged. The results demonstrate that NO-clamping augments sodium excretion in response to volume expansion at constant MABP and GFR, reduced RPF and decreased renin system activity, a response termed hypernatriuresis. The results indicate that mediator(s) other than MABP, RPF, GFR and renin system activity contribute significantly to the homoeostatic response to saline loading, but the specific mechanisms of hypernatriuresis remain obscure.
一氧化氮（NO）可能参与了液体的体内平衡。我们假设，NO 合成的增加会导致急性盐诱导的排钠，因此，当 NO 的可用性稳定时，这种排钠作用应该会减弱。在同时输注 L-NAME[NG-硝基-L-精氨酸甲酯；体重 750μg·kg⁻¹的推注和 8.3μg·min⁻¹·kg⁻¹的体重输注]和 SNP（硝普钠）时，我们研究了年轻男性，后者的速度可以防止 L-NAME 增加总外周阻力（“NO 钳夹”）。在没有同时进行 NO 钳夹的情况下，进行缓慢的容量扩张（盐水，20μmol 的 NaCl·min⁻¹·kg⁻¹的体重，持续 3 小时）。NO 钳夹本身降低了 RPF（肾血浆流量；P~0.02），并倾向于降低动脉血压[平均动脉血压（MABP）]。容量扩张显著降低了肾素、血管紧张素 II（AngII）和醛固酮的血浆水平（均 P<0.001），而 MABP（振荡法）、心率、心输出量（阻抗心动图）、RPF（对氨基马尿酸）、GFR[肾小球滤过率；使用 51Cr 标记的 EDTA]和血浆[Na+]和[K+]保持不变。在恒定的滤过负荷下，容量扩张增加了钠的排泄（P<0.02），但在 NO 钳夹时比在对照时更多（增加 184%，而增加 52%；P<0.0001）。在容量扩张期间，尿硝酸盐/亚硝酸盐的排泄增加；血浆 cGMP 和血浆血管加压素保持不变。结果表明，在恒定的 MABP 和 GFR、降低的 RPF 和降低的肾素系统活性下，NO 钳夹增加了对容量扩张的钠排泄，这种反应称为高钠血症。结果表明，除了 MABP、RPF、GFR 和肾素系统活性之外，其他介质显著促进了对盐水负荷的体内平衡反应，但高钠血症的具体机制仍不清楚。
