Large Blood Pressure Variability Aggravates Arteriolosclerosis and Cortical Sclerotic Changes in the Kidney in Hypertensive Rats
Large Blood Pressure Variability Aggravates Arteriolosclerosis and Cortical Sclerotic Changes in the Kidney in Hypertensive Rats
复制标题
DOI：
10.1253/circj.cj-14-0027
复制
发表时间：
2014-09-01
影响因子：
3.3
通讯作者：
Imaizumi, Tsutomu
中科院分区：
文献类型：
--
作者：
Aoki, Yuji;Kai, Hisashi;Imaizumi, Tsutomu
背景资料：在自发性高血压大鼠（SHR）中，短期血压（BP）变异性（BPV）增加通过心脏血管紧张素II（angII）系统促进高血压心脏重构。然而，对大BPV引起的肾损害知之甚少。因此，在肾脏的组织学变化进行了研究和坎地沙坦，血管紧张素II 1型受体阻滞剂（ARB），也进行了检查，看看它是否会防止大BPV.Methods和结果的SHR肾损伤：双侧窦弓去神经支配（SAD）在SHR中创建一个模型的高血压和大BPV的组合。SAD增加了BPV，但不改变平均BP。7周后，SAD诱导斑片状、楔形、局灶性硬化病变，伴有间质纤维化和皮质中肾小球和肾小管的缺血性改变。肾小球前小动脉病变与血管平滑肌细胞增殖和细胞外基质沉积有关，导致管腔狭窄和闭塞。慢性治疗与降压剂量的坎地沙坦不仅防止动脉硬化的变化，但也皮质硬化病变的SHR SAD没有改变BPV。结论：大BPV恶化肾小球前动脉硬化，导致皮质硬化的变化，SHR通过局部血管紧张素II介导的机制。这项研究提出了ARB对合并高血压和BPV增加的患者的肾脏保护有用的可能性。
Background: It has been shown that increased short-term blood pressure (BP) variability (BPV) aggravates hypertensive cardiac remodeling in spontaneously hypertensive rats (SHRs) through a cardiac angiotensin II (angII) system. However, little was known about the renal damage induced by large BPV. Thus, histological changes in the kidney were investigated and candesartan, an angII type 1 receptor blocker (ARB), was also examined to see whether it would prevent renal damage in SHRs with large BPV.Methods and Results: Bilateral sinoaortic denervation (SAD) was performed in SHRs to create a model of a combination of hypertension and large BPV. SAD increased BPV without changing mean BP. Seven weeks later, SAD induced patchy, wedge-shaped, focal sclerotic lesions accompanied by interstitial fibrosis and ischemic changes of glomeruli and tubules in the cortex. The pre-glomerular arterioles adjacent to the sclerotic lesions showed arteriolosclerotic changes associated with vascular smooth muscle cell proliferation and extracellular matrix deposition, leading to the luminal narrowing and occlusion. Chronic treatment with a subdepressor dose of candesartan prevented not only arteriolosclerotic changes but also cortical sclerotic lesions in SHRs with SAD without changing BPV.Conclusions: Large BPV aggravates pre-glomerular arteriolosclerosis, which results in the cortical sclerotic changes in SHRs through a local angII-mediated mechanism. This study raised the possibility that ARB is useful for renal protection in patients who have a combination of hypertension and increased BPV.