Peleli Maria, Al-Mashhadi Ammar, Yang Ting, Larsson Erik, Wåhlin Nils, Jensen Boye L, G Persson A Erik, Carlström Mattias
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden;
Division of Pediatric Surgery, Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden; Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden;
Am J Physiol Renal Physiol. 2016 Jan 1;310(1):F43-56. doi: 10.1152/ajprenal.00345.2015. Epub 2015 Nov 4.
Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P < 0.05) and displayed increased urine production and lower urine osmolality. The blood pressure change in response to salt loading (salt sensitivity) was more pronounced in the PUUO group compared with the control group (15 ± 2 vs. 5 ± 1 mmHg, P < 0.05). Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P < 0.05) and normalized the renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates hypertension and restores the renal excretion pattern, which is associated with reduced renal NOX and components of the renin-angiotensin-aldosterone system. This study emphasizes a link between renal nerves, the development of hypertension, and modulation of NOX function.
肾积水与盐敏感性高血压的发生有关。研究表明，交感神经活动增强和氧化应激在高血压及盐敏感性调节中起重要作用。本研究主要旨在探讨肾交感神经活动在肾积水大鼠高血压发生中的作用。此外，我们旨在研究去肾神经支配是否会影响NADPH氧化酶（NOX）的功能。在3周龄大鼠中制造部分单侧输尿管梗阻（PUUO）以诱导肾积水。同时进行假手术或去肾神经支配。在正常、高盐和低盐饮食期间测量血压。用正常盐饮食治疗后，对肾脏排泄模式、NOX活性和表达以及肾素-血管紧张素-醛固酮系统的成分进行了表征。在正常盐饮食下，PUUO组大鼠的血压高于对照组（115±3 vs. 87±1 mmHg，P<0.05），尿量增加，尿渗透压降低。与对照组相比，PUUO组对盐负荷的血压变化（盐敏感性）更明显（15±2 vs. 5±1 mmHg，P<0.05）。PUUO大鼠去肾神经支配可减轻高血压（97±3 mmHg）和盐敏感性（5±1 mmHg，P<0.05），并使肾脏排泄模式正常化，而肾纤维化和炎症程度未改变。PUUO大鼠肾皮质中的NOX活性和表达以及肾素和血管紧张素II 型1A受体表达增加，而去神经支配使其正常化。PUUO大鼠血浆Na(+)和K(+)水平升高，去肾神经支配后恢复正常。最后，PUUO大鼠去神经支配还与心脏中NOX表达降低、超氧化物生成减少和纤维化有关。总之，去肾神经支配可减轻高血压并恢复肾脏排泄模式，这与肾脏NOX及肾素-血管紧张素-醛固酮系统成分减少有关。本研究强调了肾神经、高血压发生与NOX功能调节之间的联系。
