Gattone Vincent H, Siqueira Tibério M, Powell Charles R, Trambaugh Chad M, Lingeman James E, Shalhav Arieh L
Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA.
Exp Biol Med (Maywood). 2008 Aug;233(8):952-7. doi: 10.3181/0802-RM-54. Epub 2008 May 14.
The kidney has both afferent (sensory) and efferent (sympathetic) nerves that can influence renal function. Renal innervation has been shown to play a role in the pathogenesis of many forms of hypertension. Hypertension and flank pain are common clinical manifestations of autosomal dominant (AD) polycystic kidney disease (PKD). We hypothesize that renal innervation contributes to the hypertension and progression of cystic change in rodent PKD. In the present study, the contribution of renal innervation to hypertension and progression of renal histopathology and dysfunction was assessed in male Han:SPRD-Cy/+ rats with ADPKD. At 4 weeks of age, male offspring from crosses of heterozygotes (Cy/+) were randomized into either 1) bilateral surgical renal denervation, 2) surgical sham denervation control, or 3) nonoperated control groups. A midline laparotomy was performed to allow the renal denervation (i.e., physical stripping of the nerves and painting the artery with phenol/alcohol). Blood pressure (tail cuff method), renal function (BUN) and histology were assessed at 8 weeks of age. Bilateral renal denervation reduced the cystic kidney size, cyst volume density, systolic blood pressure, and improved renal function (BUN) as compared with nonoperated controls. Operated control cystic rats had kidney weights, cyst volume densities, systolic blood pressures, and plasma BUN levels that were intermediate between those in the denervated animals and the nonoperated controls. The denervated group had a reduced systolic blood pressure compared with the operated control animals, indicating that the renal innervations was a major contributor to the hypertension in this model of ADPKD. Renal denervation was efficacious in reducing some pathology, including hypertension, renal enlargement, and cystic pathology. However, sham operation also affected the cystic disease but to a lesser extent. We hypothesize that the amelioration of hypertension in Cy/+ rats was due to the effects of renal denervation on the renin angiotensin system.
肾脏具有传入（感觉）神经和传出（交感）神经，它们均可影响肾功能。肾神经支配已被证明在多种形式的高血压发病机制中起作用。高血压和胁腹痛是常染色体显性（AD）多囊肾病（PKD）的常见临床表现。我们假设肾神经支配会导致啮齿动物PKD的高血压和囊肿变化进展。在本研究中，我们在患有ADPKD的雄性Han:SPRD-Cy/+大鼠中评估了肾神经支配对高血压以及肾脏组织病理学和功能障碍进展的影响。在4周龄时，将杂合子（Cy/+）杂交产生的雄性后代随机分为三组：1）双侧手术去肾神经组，2）手术假去神经对照组，或3）非手术对照组。进行中线剖腹术以实施去肾神经操作（即物理剥离神经并用苯酚/酒精涂抹动脉）。在8周龄时评估血压（尾袖法）、肾功能（血尿素氮）和组织学。与非手术对照组相比，双侧去肾神经减少了多囊肾的大小、囊肿体积密度、收缩压，并改善了肾功能（血尿素氮）。手术对照囊肿大鼠的肾脏重量、囊肿体积密度、收缩压和血浆血尿素氮水平介于去神经动物和非手术对照组之间。与手术对照动物相比，去神经组的收缩压降低，表明肾神经支配是该ADPKD模型中高血压的主要促成因素。去肾神经在减轻一些病理状况方面是有效的，包括高血压、肾脏肿大和囊肿病理。然而，假手术也对囊肿疾病有影响，但程度较小。我们假设Cy/+大鼠高血压的改善是由于去肾神经对肾素血管紧张素系统的作用。
