Schnackenberg C G, Tabor B L, Strong M H, Granger J P
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216, USA.
Am J Physiol. 1997 Mar;272(3 Pt 2):R879-86. doi: 10.1152/ajpregu.1997.272.3.R879.
Because endothelium-derived factors are known to have multiple actions throughout the body, the role of nitric oxide (NO) produced within the kidney in the regulation of renin release is still unclear. Therefore, the objectives of this study were to determine the effect of local NO synthesis inhibition within the kidney on renin secretion rate (RSR) and to determine whether the macula densa mechanism mediates the effect of NO on renin secretion rate in dogs. The NO synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) was administered via the renal artery at 5 microg x kg(-1) x min(-1) to dogs with normal kidney function and to dogs with the macula densa mechanism blocked, established by using the nonfiltering kidney model. In dogs with normal kidney function, renal arterial pressure (RAP) and glomerular filtration rate (GFR) remained constant throughout the experiment (131 +/- 5 mmHg and 22.6 +/- 3.0 ml/min, respectively). However, intrarenal NO synthesis inhibition decreased renal blood flow (RBF) by 16% (240 +/- 22 to 201 +/- 23 ml/min) and increased renal vascular resistance (RVR) by 24% (0.59 +/- 0.08 to 0.73 +/- 0.09 mmHg x ml(-1) x min). In addition, L-NAME decreased the fractional excretion of lithium by 27% (30.0 +/- 3.7 to 21.6 +/- 4.3%) and decreased the fractional excretion of sodium by 35% (0.86 +/- 0.29 to 0.56 +/- 0.21%). Associated with these changes in renal function, renin secretion rate increased by 194 and 235%. In marked contrast, renin secretion rate remained constant in dogs with the macula densa mechanism blocked. Intrarenal NO synthase blockade decreased RSR by 4 and 10% in dogs with the macula densa mechanism blocked. The RAP, RBF, and RVR responses to intrarenal NO synthesis inhibition in dogs with the macula densa mechanism blocked were similar to the renal hemodynamic response in dogs with normal kidney function. In summary, we have demonstrated that intrarenal NO synthesis blockade enhances renin secretion in dogs. The macula densa mechanism appears to play an important role in mediating the effect of intrarenal NO synthesis inhibition on renin release.
由于已知内皮衍生因子在全身具有多种作用，因此肾脏内产生的一氧化氮（NO）在肾素释放调节中的作用仍不清楚。因此，本研究的目的是确定肾脏内局部NO合成抑制对肾素分泌率（RSR）的影响，并确定致密斑机制是否介导NO对犬肾素分泌率的影响。通过使用无滤过功能肾模型建立了致密斑机制阻断的犬，将NO合成抑制剂N（ω）-硝基-L-精氨酸甲酯（L-NAME）以5μg·kg⁻¹·min⁻¹的剂量经肾动脉给予肾功能正常的犬和致密斑机制阻断的犬。在肾功能正常的犬中，整个实验过程中肾动脉压（RAP）和肾小球滤过率（GFR）保持恒定（分别为131±5mmHg和22.6±3.0ml/min）。然而，肾内NO合成抑制使肾血流量（RBF）降低了16%（从240±22降至201±23ml/min），肾血管阻力（RVR）增加了24%（从0.59±0.08升至0.73±0.09mmHg·ml⁻¹·min）。此外，L-NAME使锂的排泄分数降低了27%（从30.0±3.7降至21.6±4.3%），钠的排泄分数降低了35%（从0.86±0.29降至0.56±0.21%）。与这些肾功能变化相关，肾素分泌率分别增加了194%和235%。形成鲜明对比的是，在致密斑机制阻断的犬中，肾素分泌率保持恒定。在致密斑机制阻断的犬中，肾内NO合酶阻断使RSR降低了4%和10%。致密斑机制阻断的犬肾内NO合成抑制时的RAP、RBF和RVR反应与肾功能正常的犬的肾血流动力学反应相似。总之，我们证明了肾内NO合成阻断可增强犬的肾素分泌。致密斑机制似乎在介导肾内NO合成抑制对肾素释放的影响中起重要作用。
