The Effects of Olmesartan and Alfacalcidol on Renoprotection and klotho Gene Expression in 5/6 Nephrectomized Spontaneously Hypertensive Rats

Recently, an angiotensin inhibitor has been shown to upregulate theklotho mRNA level in chronic renal failure. In addition, theadministration of vitamin D has been reported to improve the mortality of patients withchronic renal failure. In this study, we examined the effects of an angiotensin inhibitorand/or vitamin D on the progression of chronic renal failure by using male 5/6nephrectomized (5/6Nx) spontaneously hypertensive rats. Male 5/6Nx spontaneouslyhypertensive rats were assigned to 4 groups as follows: 5/6Nx group, 5/6Nx rats; Alfgroup, 5/6Nx rats administered alfacalcidol (0.2 μg/kg/day); Olm group, 5/6Nx ratsadministered olmesartan (15 mg/kg/day); Alf + Olm group, 5/6Nx rats administeredalfacalcidol (0.2 μg/kg/day) and olmesartan (15 mg/kg/day). These drugs were administeredfor 12 weeks. Systolic blood pressure in the Alf, Olm and Alf + Olm groups weresignificantly decreased relative to that in the 5/6Nx group during the 12-weekexperimental period. As a result, all treated groups showed renoprotection based onimprovement of the systolic blood pressure, urinary protein excretion and histologicalrenal fibrosis. Combination therapy of alfacalcidol and olmesartan was more effective thaneither alfacalcidol or olmesartan alone. Expression of klotho mRNA wassignificantly upregulated in the Alf + Olm group in comparison with in the 5/6Nx group.Serum levels of fibroblast growth factor 23 in the Alf group and the Alf + Olm group weresignificantly higher than those in the 5/6Nx group and the Olm group. In conclusion, thecombination of Olm and Alf inhibited the progression of renal damage in the 5/6Nx groupthrough the strong antihypertensive effect as well as the upregulation of theklotho gene.     

阿托伐他汀对高血压大鼠肾脏CTGF表达的影响

目的:观察自发性高血压大鼠(SHR)肾脏结缔组织生长因子(CTGF)的表达,探讨3-羟基-3-甲基戊二酞辅酶A(HMG-CoA)还原酶抑制剂阿托伐他汀(Atorvastin)对高血压肾损害的保护作用。方法:20只12周龄雄性SHR随机分为阳性对照组和阿托伐他汀干预组各10只,药物干预组每只大鼠予以阿托伐他汀20mg/kg/天灌胃(共12周);10只12周龄雄性WKY大鼠作为正常对照组。测量不同时期各组大鼠尾动脉收缩压(SBP)、血脂、尿β2-微球蛋白(β2-MG)及肾功能指标;用免疫组织化学方法检测CTGF蛋白在各组大鼠肾脏中的表达;用RT-PCR方法检测CTGFmRNA在肾脏的表达水平。结果:⑴与正常对照组、药物干预组相比,阳性对照组血清尿素氮(BUN)、肌酐(Cr)水平无显著差异,而SBP、血脂、尿β2-MG均显著增高(P<0.01)。⑵CTGF蛋白及mRNA在阳性对照组肾脏中的表达较正常对照组明显增强,药物干预组比阳性对照组明显减少(P<0.05)。结论:CTGF表达增加可能是导致高血压肾损害的重要机制之一;阿托伐他汀通过降低血压及血脂,显著减少尿β2-MG,改善肾组织的病理变化,抑制CTGF在SHR肾脏表达而发挥对高血压肾损害的保护作用。     

加压素在自发性高血压大鼠与正常大鼠下丘脑视上核、室旁核神经元内表达

目的观察加压素(AVP)在自发性高血压大鼠(SHR)与正常大鼠下丘脑视上核(SON)、室旁核(PVN)内的分布。方法应用光镜和免疫细胞化学技术。结果SHR的AVP阳性细胞内分泌颗粒密集呈棕黄色,正常大鼠组则染色较浅。SHR大鼠SON内AVP阳性神经元百分数(69.30±18.10%)明显多于正常大鼠(59.53±16.97%,P<0.05),而两组大鼠PVN内AVP的表达无明显差异。结论AVP在下丘脑的血压调节活动中起着重要的介导作用,中枢AVP含量的异常增加可能与高血压的发病有关。     

Arthritis Induced by Adjuvant in Spontaneously Hypertensive and Normotensive Rats: Endogenous Glucocorticoid Effects on Inflammatory Response

The present study investigated arthritis induced by complete Freund adjuvant (AIA) in spontaneously hypertensive and normotensive rats (respectively, SHR and NTR rats). The inflammatory reaction was studied for 28 days by evaluating paw edema and secondary lesions found 10 days after complete Freund adjuvant (CFA) administration. The body weight of the animals and macroscopic alterations of several organs, including spleen, thymus, adrenal glands, and lymph nodes, were also analyzed. The results showed that the AIA manifestations were decreased in SHRs compared with NTRs. Moreover, this altered inflammatory response was not modified by surgical adrenalectomy.     

Bilateral Common Carotid Artery Occlusion in Spontaneously Hypertensive Rats: A Feasible Animal Model for Ocular Ischemic Syndrome

The purpose of this study was to investigate the feasibility of inducing ocular ischemic syndrome in spontaneously hypertensive rats. Hypertensive and normotensive Wistar–Kyoto rats had bilateral occlusion or sham surgery. They were divided into 4 groups: (1) hypertensive‐ischemia, (2) hypertensive‐sham, (3) normotensive‐ischemia, and (4) normotensive‐sham. Four months after the operation, the global changes of the eye and pupillary light reflex were assessed. Then each rat was perfused, and randomly one of the bulbuses oculi was prepared as retinal flat mounts for investigation of vascular changes. The opposite eyeball was prepared as a paraffin section for observation of the linear density of retinal ganglion cells and for thickness measurement. One hypertensive‐ischemia rat had a cataract in one eye and another rat in the same group had bulbus oculi collapse in one eye. The light reflex disappeared in 13.33% of hypertensive‐ischemia rats, and the rest of the hypertensive‐ischemia rats and normotensive‐ischemia rats had slow reflex. Compared with the respective controls, the peripheral retinal vascular network in hypertensive‐ischemia and normotensive‐ischemia rats was sparse; linear density of the retinal ganglion cells was significantly reduced; and the retinal thickness was reduced. Compared with normotensive‐ischemia rats, the hypertensive‐ischemia rats demonstrated more severe changes. After bilateral common carotic artery occlusion, the eyes of hypertensive rats developed various pathological changes similar to those of ocular ischemic syndrome. In conclusion, an animal model for ocular ischemic syndrome can be created by bilateral common carotid artery occlusion in spontaneously hypertensive rats. Anat Rec, 299:806–814, 2016. © 2016 Wiley Periodicals, Inc.     

Acute Immune and Non-Immune Inflammatory Response in Spontaneously Hypertensive Rats and Normotensive Rats. Role of Endogenous Nitric Oxide

Summary The present study investigated the acute inflammatory response (increase in vascular permeability and leukocytes migration) in the pleura of spontaneously hypertensive rats (SHR) and normotensive rats (NTR), using two different stimulus: carrageenan and active anaphylaxis. In addition, the role of endogenous nitric oxide in these responses was investigated. Results The inflammatory response induced by intrapleural carrageenan injection in SHR developed similarly to that in NTR. Treatment with L-NAME, reduced the intensity of this response in both groups of rats. The inflammatory response induced by active anaphylaxis in SHR and NTR was different. The increase in vascular permeability occurred later in the SHR compared to NTR. The number of leukocyte present in inflammatory exudates was increased at 4 h in both groups of rats. L-NAME treatment did not inhibit exudation at the intervals under analysis, however, reduced the number of mononuclear cells in the inflammatory exudate of SHR. Conclusion The development of the inflammatory response in SHR differs from that in NTR, depending on the nature of the inflammatory stimulus. Endogenous NO plays a clear role in carrageenan-induced inflamma-tion, but not in immunologically mediated inflammation in the analyzed period.     

氯沙坦逆转高血压大鼠阻力血管重塑的实验研究

目的:探讨氯沙坦对自发性高血压大鼠(SHR)阻力血管重塑的影响。方法:将雄性SHR20只随机分为氯沙坦治疗组和SHR对照组。另选同系雄性WKY大鼠10只作为正常对照组。治疗组给予氯沙坦30mg/kg/天,溶于饮水灌胃治疗17周。颈动脉插管,心电血流动力学监护仪测定动脉收缩压,应用计算机图像分析,计算血管壁腔面积比,用光镜和透射电镜观察SHR肠系膜动脉三级分支结构的变化;血浆放免法测肾素活性和血管紧张素Ⅱ(AngⅡ)含量。结果:氯沙坦治疗组的血管壁腔面积比与SHR对照组相比有所降低(P<0.05),但与WKY相比有所升高(P<0.05);血浆肾素活性在WKY组和SHR对照组之间无明显差异(P>0.05),治疗组肾素活性高于SHR对照组(P<0.05);治疗组的AngⅡ水平高于SHR对照组(P<0.01)。结论:氯沙坦具有逆转SHR血管重塑的作用。     

Olmesartan restores the protective effect of remote ischemic perconditioning against myocardial ischemia/reperfusion injury in spontaneously hypertensive rats

OBJECTIVES:Remote ischemic perconditioning is the newest technique used to lessen ischemia/reperfusion injury. However, its effect in hypertensive animals has not been investigated. This study aimed to examine the effect of remote ischemic perconditioning in spontaneously hypertensive rats and determine whether chronic treatment with Olmesartan could influence the effect of remote ischemic perconditioning.METHODS:Sixty rats were randomly divided into six groups: vehicle-sham, vehicle-ischemia/reperfusion injury, vehicle-remote ischemic perconditioning, olmesartan-sham, olmesartan-ischemia/reperfusion and olmesartan-remote ischemic perconditioning. The left ventricular mass index, creatine kinase concentration, infarct size, arrhythmia scores, HIF–1α mRNA expression, miR-21 expression and miR-210 expression were measured.RESULTS:Olmesartan significantly reduced the left ventricular mass index, decreased the creatine kinase concentration, limited the infarct size and reduced the arrhythmia score. The infarct size, creatine kinase concentration and arrhythmia score during reperfusion were similar for the vehicle-ischemia/reperfusion group and vehicle-remote ischemic perconditioning group. However, these values were significantly decreased in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. HIF–1α, miR-21 and miR-210 expression were markedly down-regulated in the Olmesartan-sham group compared to the vehicle-sham group and significantly up-regulated in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group.CONCLUSION:The results indicate that ¹ the protective effect of remote ischemic perconditioning is lost in vehicle-treated rats and that chronic treatment with Olmesartan restores the protective effect of remote ischemic perconditioning; ² chronic treatment with Olmesartan down-regulates HIF–1α, miR-21 and miR-210 expression and reduces hypertrophy, thereby limiting ischemia/reperfusion injury; and ³ recovery of the protective effect of remote ischemic perconditioning is related to the up-regulation of HIF–1α, miR-21 and miR-210 expression.     

Influence of sympathetic and AT1‐receptor blockade on angiotensin II and adrenergic agonist‐induced renal vasoconstrictions in spontaneously hypertensive rats

Aim: This study investigated the influence of angiotensin II (Ang II) receptor and adrenergic blockade on the renal vasoconstrictions caused by Ang II and adrenergic agonists in spontaneously hypertensive rats (SHR). Methods: Forty‐eight SHR were subjected to 7 days of losartan (10 mg kg^?1 day^?1 p.o.), carvedilol (5 mg kg^?1 day^?1 p.o.) or losartan + carvedilol (10 mg kg^?1 day^?1 + 5 mg kg^?1 day^?1 p.o.). On day 8, the rats were anaesthetized and renal vasoconstrictor experiments performed. One group of rats underwent acute unilateral renal denervation. Results: There were significant (P < 0.05) reductions in the renal vasoconstrictor responses to noradrenaline, phenylephrine, methoxamine and Ang II after losartan and carvedilol treatments compared with that in untreated rats (all P < 0.05). However, in renally denervated SHR treated with carvedilol, the vasoconstrictor responses to all the vasoactive agents were enhanced compared with those in SHR with intact renal nerves treated with carvedilol. Intact SHR given both losartan and carvedilol showed greater renal vasoconstrictor responses to the vasoactive agents than when given either losartan or carvedilol alone (all P < 0.05). Conclusion: Carvedilol reduced the vasoconstrictor response to Ang II and all the adrenergic agonists in the presence of the renal nerves, but, following the removal of renal sympathetic activity, carvedilol enhanced the sensitivity of both renal α₁‐adrenoceptors and AT₁ receptors to the vasoactive agents. Co‐treatment with losartan and carvedilol reduced the renal vasoconstrictor responses to exogenously administered vasoactive agents but to a lesser extent than losartan or carvedilol alone. The results obtained demonstrate an interaction between Ang II receptors and adrenergic neurotransmission in the SHR.     

氯沙坦对自发性高血压大鼠主动脉内膜ICAM-1和PAI-1表达的影响

目的 :比较早期雄性自发性高血压大鼠 (SHR)和正常雄性同周龄WistarKyoto大鼠 (WKY)主动脉内膜细胞间粘附分子 1(ICAM 1)和纤溶酶原激活物抑制剂 1(PAI 1)的表达及氯沙坦对其的影响。方法 :将 2 0只雄性SHR随机分成二组 ,每组 10只 ,其中一组灌喂氯沙坦 2 0mg/kg/天 ,另一对照组给正常饮水 ,共 12周 ,并与WKY 10只比较。采用免疫组织化学方法检测三组大鼠主动脉内膜ICAM 1和PAI 1的表达。结果 :与WKY大鼠比较 ,SHR对照组主动脉内膜ICAM 1和PAI 1表达明显增高 ;经氯沙坦治疗 12周后SHR血压显著降低 ,主动脉内膜ICAM 1和PAI 1表达亦明显下降。结论 :氯沙坦在有效降压的同时也明显抑制SHR主动脉内膜ICAM 1和PAI 1的表达 ,提示氯沙坦作为血管紧张素II受体 1拮抗剂 (AT1 R)在抗高血压并发症发生中起一定的作用     

Effects of Aqueous Extract of Lycopersicum esculentum L. var. “Camone” Tomato on Blood Pressure,Behavior and Brain Susceptibility to Oxidative Stress in Spontaneously Hypertensive Rats

Behavioral disorders affect millions of people worldwide. Hypertension contributes to both the development and progression of brain damage and cognitive dysfunction and could represent the most powerful modifiable risk factor for cerebral vessel dysfunction and consequent behavioral impairment. Tomato contains antioxidants and bioactive molecules that might play an important role in the prevention of cardiovascular and brain diseases. The effects of the combined gel and serum from Lycopersicum esculentum L. var. “Camone” tomatoes and those of purified tomato glycoalkaloids (tomatine) and an antihypertensive drug (captopril) were investigated in male spontaneously hypertensive rats (SHRs) and compared with normotensive Wistar Kyoto (WKY) rats. Body weight, systolic blood pressure, behavioral parameters, as well as brain susceptibility to oxidative stress and brain cytokine contents, were assessed. Treating hypertensive rats with tomato gel/serum or captopril for four weeks caused a significant reduction in blood pressure, decreased locomotor activity and increased grooming behavior; the last two parameters were also significantly affected by tomatine treatment. Brain slices obtained from hypertensive rats treated with tomato gel/serum were more resistant to oxidative stress and contained lower levels of inflammatory cytokines than vehicle-treated ones. In contrast, tomatine treatment had no effect. In conclusion, the tomato-derived gel/serum can be considered a dietary supplement able to drive in vivo blood pressure towards healthier values and also control some central effects such as behavior and brain oxidative stress.     

缬沙坦及苯那普利对慢性肾功能衰竭大鼠左室肥厚的影响

目的：观察并比较缬沙坦及苯那普利对慢性肾功能衰竭大鼠左室肥厚的影响，探讨其作用机制。方法：选用SD雄性大鼠30只，通过5/6肾切除法复制慢性肾功能衰竭模型，术后2周随机分为模型组、缬沙坦组及苯那普利组，并设假手术组作为对照。术后第6周末各组大鼠进行血压及肾功能（Scr、BUN）的测定；处死大鼠，取出心脏进行病理组织形态学观察，并采用免疫组织化学方法检测心肌转化生长因子β₁（TGF-β₁）及纤维连接蛋白（FN）的表达。结果：模型组术后第6周收缩压、左室重量指数（LVMI）及室间隔厚度明显高于假手术组，缬沙坦及苯那普利组收缩压、LVMI及室间隔厚度均低于模型组（P＜0.01或P＜0.05）；免疫组化染色显示，缬沙坦组及苯那普利组大鼠心肌TGF-β₁、FN表达均较模型组减少（P＜0.01）。结论：缬沙坦及苯那普利能减轻慢性肾功能衰竭大鼠的左室肥厚，其作用机制可能是通过下调心肌TGF-β₁、FN表达来实现的。     

抗血管紧张素Ⅱ1型受体抗体对自发性高血压大鼠血压和肾脏的影响

目的观察血管紧张素Ⅱ1型受体(AT1受体)胞外不同肽段主动免疫对自发性高血压大鼠(SHR)血压和肾脏的影响。方法人工合成的AT1受体胞外肽段主动免疫SHR。动态监测SHR血压变化,观察肾脏组织病理变化,RT-PCR法检测肾脏组织原癌基因表达水平。结果ATR12181组血压为(179.0±13.6)mmHg较对照组(188.0±9.9)mmHg下降(P<0.05)。ATR12181组相比对照组肾脏病理变化减轻,ATR11188组相比对照组病变加重。ATR12181组cf-os、cj-un表达水平明显低于对照组(P<0.05),ATR11188组则明显高于对照组(P<0.05)。结论不同肽段免疫产生的不同抗体对SHR血压和肾脏可产生不同的影响。     

辛伐他汀对高血压大鼠主动脉NF-κB和MCP-1表达的影响

目的研究他汀类药物对核因子κB(NF -κB)、单核细胞趋化蛋白 -1(MCP -1)在自发性高血压大鼠 (SHR)大血管中表达的影响 ,探讨其预防动脉粥样硬化 (AS)的可能机制。方法20只12周龄雄性SHR随机分为SHR组和辛伐他汀 (simvastatin)组,simvastatin组用simvastatin5mg/kg·d灌胃8周 ,另取10只同龄雄性京都种Wistar大鼠为WKY组 ,免疫组化测各组主动脉NF -κB、MCP-1的表达 ,ELISA测血清MCP-1含量。结果SHR组主动脉组织中NF-κB、MCP-1表达及血清MCP-1含量显著增加 (P<0.01) ,且MCP -1表达与NF -κB活化正相关(r=0.728,P<0.01) ;simvastatin组NF -κB、MCP -1表达和血清MCP -1含量显著降低 (P<0.01)。SHR组及simvastatin组之间血压及血清总胆固醇、总甘油三脂水平无明显差异(P>0.05)。结论他汀类药物可能独立于降脂外部分通过抑制NF-κB的活化来调控MCP-1表达而抗AS。     

Blood Serum Levels of IL-2, IL-6, IL-8, TNF-α and IL-1β in Patients on Maintenance Hemodialysis

Cytokines are essential mediators of immune response and inflammatory reactions. Patients with chronic renal failure (CRF) commonly present with abnormalities of immune function related with impaired kidney function and the accumulation of uremic toxins in addition to bioincompatibility of dialyzer membranes. During a hemodialysis (HD) session, cytokines are released mainly by monocytes activated by endotoxin-type compounds in dialyzer fluid, complement factors and direct contact with dialyzer membrane. The study included 15 CRF patients, aged 36.4±2.9 years, on regular HD maintenance therapy for mean 68±10 months and 15 healthy controls. It was designed to assess serum levels of a panel of inflammatory cytokines: IL-1β, IL-2, IL-6, IL-8 and TNF-αin CRF patients on regular maintenance HD before, 20, 60 and 240 minutes of a single HD session in parallel with C-reactive protein (CRP) as an additional parameter. CRP concentration was increased in HD patients when compared with healthy controls. The concentrations of IL-1, IL-6, IL-8 and TNF-αwere increased, whereas the serum level of IL-2 was not altered during a single HD session.     

高血压鼠脑底动脉神经肽Y能神经与颈上神经节、星状神经节的关系

目的　探讨高血压鼠脑底动脉神经肽Y能神经与颈上神经节、星状神经节的关系。方法　应用神经节切除术和免疫组织化学ABC法 ,对 16只自发性高血压鼠脑底动脉神经肽Y能神经纤维的分布进行了观察。结果　对照组自发性高血压鼠大脑前动脉、大脑中动脉、大脑后动脉和基底动脉壁上均可见神经肽Y能阳性纤维 ,纤维似曲线状 ,多呈网状走行 ,密度较高。手术Ⅰ组作双侧颈上神经节切除术 ,脑底主要动脉的阳性纤维明显减少 ;手术Ⅱ组作双侧星状神经节切除 ,脑底主要动脉壁上的阳性纤维明显减少 ;手术Ⅲ组作双侧颈上神经节和星状神经节切除术 ,脑底主要动脉的阳性纤维完全消失。结论　自发性高血压鼠脑底主要动脉的神经肽Y能神经纤维起源于双侧颈上神经节和双侧星状神经节 ,神经肽Y能神经可能在高血压发病中起作用     

迷走神经刺激对戊四氮致痫大鼠丘脑网状核NMDAR1 mRNA和GABAARα1 mRNA的影响

为探讨迷走神经刺激（Vagus nerve stimulation,VNS)抗癫痫的作用机制。应用原位杂交组织化学及图像分析方法研究戊四氮（Pentylenetetrazol,PTZ)致痫大鼠丘脑网状核谷氨酸受体NMDAR1mRNA和γ-氨基丁酸A受体（GABAAR）α1亚单位mRNA的变化。结果显示，PTZ致痫组大鼠丘脑网状核NMDAR1mRNA表达明显高于正常对照组，而VNS抗癫痫组明显低于PTZ致癫痫组，与之相反，PTZ致癫痫组GABAARα1mRNA的表达明显低于正常对照组，VNS抗癫痫组明显高于PTZ致癫痫组，上述结果表明，VNS可能通过抑制丘脑网状核兴奋的神经递质受体NM-DAR的活动和增强抑制性神经递质受体γ-氨基丁酸受体GABAAR的活动，降低大脑皮层的兴奋性，抑制癫痫的发生和发展。     

Upregulation of the brain renin-angiotensin system in rats with chronic renal failure

Aim: We investigated how the brain renin–angiotensin system is involved in regulation of the sympathetic activity and arterial pressure in rats with chronic renal failure. Methods: Systolic arterial pressure, heart rate and diurnal urinary noradrenaline excretion were measured for 12 weeks in spontaneously hypertensive rats (SHR) with or without subtotal nephrectomy. Expression of mRNAs related to the brain renin–angiotensin system was measured using polymerase chain reaction. Effects of a 6‐day intracerebroventricular infusion of a type 1 angiotensin II receptor antagonist (candesartan) or bilateral dorsal rhizotomy on these variables were also investigated. Results: Systolic arterial pressure and urinary excretion of noradrenaline were consistently higher in subtotally nephrectomized SHR than in sham‐operated SHR (262 ± 5 vs. 220 ± 3 mmHg, P < 0.001; 2.71 ± 0.22 vs. 1.69 ±0.19 ng g^?1 body weight day^?1, P < 0.001). Expression of renin, angiotensin‐converting enzyme and type 1 angiotensin II receptor mRNAs in the hypothalamus and lower brainstem was greater in subtotally nephrectomized SHR than in sham‐operated SHR. Continuous intracerebroventricular infusion of candesartan attenuated hypertension and the increase in urinary noradrenaline excretion in subtotally nephrectomized SHR. Dorsal rhizotomy decreased arterial pressure, urinary excretion of noradrenaline and expression of renin–angiotensin system‐related mRNAs in brains of subtotally nephrectomized SHR. Conclusion: The brain renin–angiotensin system in subtotally nephrectomized SHR appears to be activated via afferent nerves from the remnant kidney, resulting in sympathetic overactivity and hypertension in this chronic renal failure model.     

Alkali Therapy Attenuates the Progression of Kidney Injury via Na/H Exchanger Inhibition in 5/6 Nephrectomized Rats

Metabolic acidosis is a cause of renal disease progression, and alkali therapy ameliorates its progression. However, there are few reports on the role of renal acid-base transporters during alkali therapy. We evaluated the effect of sodium bicarbonate therapy and the role of acid-base transporters on renal disease progression in rats with a remnant kidney. Sprague-Dawley rats consumed dietary sodium bicarbonate (NaHCO₃) or sodium chloride (NaCl) with 20% casein after a 5/6 nephrectomy. After being provided with a casein diet, the NaHCO₃-treated group had higher levels of serum bicarbonate than the control group. At week 4, the glomerular filtration rate in the NaHCO₃ group was higher than that in the NaCl group, and the difference became prominent at week 10. The glomerulosclerosis and tubulointerstitial damage indices in the NaHCO₃ group were less severe compared with controls at week 4 and 10. The expression of the Na/H exchanger (NHE) was decreased, and apical reactivity was decreased in the NaHCO₃ group, compared with the NaCl group. Endothelin-1 levels in the kidney were also decreased in the NaHCO₃ group. Dietary sodium bicarbonate has the effects of ameliorating renal disease progression, which may be related to the altered expression of NHE in the remaining kidney.

Graphical Abstract

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