Regulation of renal hemodynamics and BP via tubuloglomerular feedback (TGF) may be an important adaptive mechanism during pregnancy. Because the β-splice variant of nitric oxide synthase 1 (NOS1β) in the macula densa is a primary modulator of TGF, we evaluated its role in normal pregnancy and gestational hypertension in a mouse model. We hypothesized that pregnancy upregulates NOS1β in the macula densa, thus blunting TGF, allowing the GFR to increase and BP to decrease.

We used sophisticated techniques, including microperfusion of juxtaglomerular apparatus in vitro, micropuncture of renal tubules in vivo, clearance kinetics of plasma FITC-sinistrin, and radiotelemetry BP monitoring, to determine the effects of normal pregnancy or reduced uterine perfusion pressure (RUPP) on macula densa NOS1β/NO levels, TGF responsiveness, GFR, and BP in wild-type and macula densa–specific NOS1 knockout (MD-NOS1KO) mice.

Macula densa NOS1β was upregulated during pregnancy, resulting in blunted TGF, increased GFR, and decreased BP. These pregnancy-induced changes in TGF and GFR were largely diminished, with a significant rise in BP, in MD-NOS1KO mice. In addition, RUPP resulted in a downregulation in macula densa NOS1β, enhanced TGF, decreased GFR, and hypertension. The superimposition of RUPP into MD-NOS1KO mice only caused a modest further alteration in TGF and its associated changes in GFR and BP. Finally, in African green monkeys, renal cortical NOS1β expression increased in normotensive pregnancies, but decreased in spontaneous gestational hypertensive pregnancies.

Macula densa NOS1β plays a critical role in the control of renal hemodynamics and BP during pregnancy.

通过管球反馈 (TGF) 调节肾血流动力学和血压可能是妊娠期间重要的适应性机制。由于致密斑中一氧化氮合酶 1 (NOS1β) 的 β 剪接变体是 TGF 的主要调节剂，我们在小鼠模型中评估了它在正常妊娠和妊娠高血压中的作用。我们假设妊娠会上调致密斑中的 NOS1β，从而减弱 TGF，从而使 GFR 升高和 BP 降低。

我们使用复杂的技术，包括体外微灌注肾小球旁装​​置、体内肾小管微穿刺、血浆 FITC-sinistrin 清除动力学和无线电遥测血压监测，以确定正常妊娠或降低子宫灌注压 (RUPP) 对黄斑的影响野生型和致密斑部特异性 NOS1 敲除 (MD-NOS1KO) 小鼠的致密斑 NOS1β/NO 水平、TGF 反应性、GFR 和血压。

致密斑 NOS1β 在妊娠期间上调，导致 TGF 减弱、GFR 升高和血压降低。在 MD-NOS1KO 小鼠中，这些妊娠引起的 TGF 和 GFR 变化大大减少，血压显着升高。此外，RUPP 导致致密斑 NOS1β 下调、TGF 增强、GFR 降低和高血压。将 RUPP 叠加到 MD-NOS1KO 小鼠中只会导致 TGF 的适度进一步改变及其 GFR 和 BP 的相关变化。最后，在非洲绿猴中，肾皮质 NOS1β 表达在正常血压妊娠中增加，但在自发性妊娠高血压妊娠中减少。

致密斑 NOS1β 在妊娠期间控制肾血流动力学和血压方面起着关键作用。