From the Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion (H.Z., X.L.).
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha (K.K., K.P.P.).
Hypertension. 2018 Sep;72(3):667-675. doi: 10.1161/HYPERTENSIONAHA.118.11071.
Renal denervation (RDN) has been shown to restore endogenous neuronal nitric oxide synthase (nNOS) in the paraventricular nucleus (PVN) and reduce sympathetic drive during chronic heart failure (CHF). The purpose of the present study was to assess the contribution of afferent renal nerves to the nNOS-mediated sympathetic outflow within the PVN in rats with CHF. CHF was induced in rats by ligation of the left coronary artery. Four weeks after surgery, selective afferent RDN (A-RDN) was performed by bilateral perivascular application of capsaicin on the renal arteries. Seven days after intervention, nNOS protein expression, nNOS immunostaining signaling, and diaphorase-positive stained cells were significantly decreased in the PVN of CHF rats, changes that were reversed by A-RDN. A-RDN reduced basal lumbar sympathetic nerve activity in rats with CHF (8.5%±0.5% versus 17.0%±1.2% of max). Microinjection of nNOS inhibitor L-NMMA (L-N-monomethyl arginine citrate) into the PVN produced a blunted increase in lumbar sympathetic nerve activity in rats with CHF. This response was significantly improved after A-RDN (Δ lumbar sympathetic nerve activity: 25.7%±2.4% versus 11.2%±0.9%). Resting afferent renal nerves activity was substantially increased in CHF compared with sham rats (56.3%±2.4% versus 33.0%±4.7%). These results suggest that intact afferent renal nerves contribute to the reduction of nNOS in the PVN. A-RDN restores nNOS and thus attenuates the sympathoexcitation. Also, resting afferent renal nerves activity is elevated in CHF rats, which may highlight a crucial neural mechanism arising from the kidney in the maintenance of enhanced sympathetic drive in CHF.
肾脏去神经支配（RDN）已被证明可恢复慢性心力衰竭（CHF）时室旁核（PVN）中的内源性神经元型一氧化氮合酶（nNOS）并降低交感神经驱动。本研究的目的是评估传入肾神经对 CHF 大鼠 PVN 中 nNOS 介导的交感神经传出的贡献。通过结扎左冠状动脉在大鼠中诱导 CHF。手术后 4 周，通过在肾动脉上进行双侧血管周应用辣椒素来进行选择性传入 RDN（A-RDN）。干预 7 天后，CHF 大鼠 PVN 中的 nNOS 蛋白表达、nNOS 免疫染色信号和黄递酶阳性染色细胞明显减少，A-RDN 逆转了这些变化。A-RDN 降低了 CHF 大鼠的基础腰交感神经活动（8.5%±0.5%对 17.0%±1.2%的最大值）。将 nNOS 抑制剂 L-NMMA（L-N-单甲基精氨酸柠檬酸盐）微注射到 PVN 中会使 CHF 大鼠的腰交感神经活动增加减弱。A-RDN 后，这种反应明显改善（Δ腰交感神经活动：25.7%±2.4%对 11.2%±0.9%）。与假手术大鼠相比，CHF 大鼠的静息传入肾神经活动显著增加（56.3%±2.4%对 33.0%±4.7%）。这些结果表明完整的传入肾神经有助于减少 PVN 中的 nNOS。A-RDN 恢复了 nNOS，从而减弱了交感兴奋。此外，CHF 大鼠的静息传入肾神经活动升高，这可能突出了肾脏中增强的交感神经驱动维持中的一个关键神经机制。
