Cardiovascular Division, Department of Physiology, School of Medicine, Federal University of Sao Paulo, Sao Paulo 04023-060, Brazil.
Faculty of Medicine, Municipal University of São Caetano do Sul, Sao Paulo 01327-000, Brazil.
Int J Mol Sci. 2024 Jun 26;25(13):6962. doi: 10.3390/ijms25136962.
The Goldblatt model of hypertension (2K-1C) in rats is characterized by renal sympathetic nerve activity (rSNA). We investigated the effects of unilateral renal denervation of the clipped kidney (DNX) on sodium transporters of the unclipped kidneys and the cardiovascular, autonomic, and renal functions in 2K-1C and control (CTR) rats. The mean arterial pressure (MAP) and rSNA were evaluated in experimental groups. Kidney function and NHE3, NCC, ENaCβ, and ENaCγ protein expressions were assessed. The glomerular filtration rate (GRF) and renal plasma flow were not changed by DNX, but the urinary (CTR: 0.0042 ± 0.001; 2K-1C: 0.014 ± 0.003; DNX: 0.005 ± 0.0013 mL/min/g renal tissue) and filtration fractions (CTR: 0.29 ± 0.02; 2K-1C: 0.51 ± 0.06; DNX: 0.28 ± 0.04 mL/min/g renal tissue) were normalized. The Na/H exchanger (NHE3) was reduced in 2K-1C, and DNX normalized NHE3 (CTR: 100 ± 6; 2K-1C: 44 ± 14, DNX: 84 ± 13%). Conversely, the Na/Cl cotransporter (NCC) was increased in 2K-1C and was reduced by DNX (CTR: 94 ± 6; 2K-1C: 144 ± 8; DNX: 60 ± 15%). In conclusion, DNX in Goldblatt rats reduced blood pressure and proteinuria independently of GRF with a distinct regulation of NHE3 and NCC in unclipped kidneys.
高血压的 Goldblatt 模型(2K-1C)在大鼠中表现为肾交感神经活性(rSNA)。我们研究了单侧 clipped 肾脏去神经支配(DNX)对未 clipped 肾脏钠转运体以及 2K-1C 和对照(CTR)大鼠心血管、自主和肾功能的影响。在实验组评估了平均动脉压(MAP)和 rSNA。评估了肾功能和 NHE3、NCC、ENaCβ和 ENaCγ 蛋白表达。DNX 没有改变肾小球滤过率(GRF)和肾血浆流量,但尿(CTR:0.0042±0.001;2K-1C:0.014±0.003;DNX:0.005±0.0013mL/min/g 肾组织)和滤过分数(CTR:0.29±0.02;2K-1C:0.51±0.06;DNX:0.28±0.04mL/min/g 肾组织)正常化。在 2K-1C 中,Na/H 交换器(NHE3)减少,DNX 使 NHE3 正常化(CTR:100±6;2K-1C:44±14,DNX:84±13%)。相反,Na/Cl 共转运蛋白(NCC)在 2K-1C 中增加,DNX 使其减少(CTR:94±6;2K-1C:144±8;DNX:60±15%)。总之,在 Goldblatt 大鼠中,DNX 独立于 GRF 降低血压和蛋白尿,同时对未 clipped 肾脏中的 NHE3 和 NCC 进行明显调节。