维甲酸对肾间质纤维化大鼠肾间质结缔组织生长因子表达的影响

目的探讨全反式维甲酸对肾间质纤维化大鼠肾间质结缔组织生长因子(CTGF)的影响及其可能机制.方法采用单侧输尿管结扎(UUO)大鼠模型.将40只SD大鼠随机分为5组:假手术组(A组)、UUO组(B组)、UUO 苯那普利组(C组)、UUO 维甲酸小剂量组(D组)、UUO 维甲酸大剂量组(E组).于造模前1d分别给C、D、E组苯那普利10mg/(kg·d)、全反式维甲酸10mg/(kg·d)和20mg/(kg·d).A、B组给予同等剂量的生理盐水.于术后第14d取术侧肾组织行HE、Masson染色评定各组肾小管间质损害程度,免疫组织化学半定量检测各组肾间质CTGF、转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)及Ⅲ型胶原(colⅢ)的表达.结果各造模组CTGF、TGF-β1、α-SMA及colⅢ的表达及肾小管间质损伤指数明显高于A组(P＜0.05),而全反式维甲酸或苯那普利均能明显抑制此变化.结论维甲酸及苯那普利可能通过下调CTGF而减轻肾间质纤维化.     

肾康注射液对单侧输尿管梗阻大鼠肾间质纤维化的影响

目的研究肾康注射液对梗阻性肾病大鼠肾小管间质纤维化的防治作用。方法采用单侧输尿管梗阻(UUO)诱导肾间质纤维化的动物模型,以血管紧张素Ⅱ受体拮抗剂(ARB)作为阳性对照,将大鼠随机分为:模型组(UUO)、肾康组、缬沙坦组,术后第14天处死大鼠,收集血清测定肌酐、尿素氮水平,肾组织用HE染色及免疫组化半定量检测各组肾间质的α-平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)的表达。结果肾康组、缬沙坦组的肾小管间质TGF-β1、α-SMA的表达均明显低于UUO组;两治疗组组间比较,肾康组对TGF-β1、α-SMA表达的抑制作用同于缬沙坦组。结论中药肾康可减轻肾间质纤维化。     

绞股蓝总皂甙对单侧输尿管结扎大鼠肾组织结缔组织生长因子表达的影响

目的:研究绞股蓝总皂甙(GPs)对单侧输尿管结扎(UUO)大鼠肾组织结缔组织生长因子(CTGF)表达及肾间质纤维化的影响。方法:采用UUO大鼠模型,将大鼠随机分为4组:假手术组、模型组、GPs组、缬沙坦组。假手术组和模型组仅给予标准饲料30g,GPs组和缬沙坦组于术前3d至术后9d每天分别给予GPs200mg/(kg·d)、缬沙坦24mg/(kg·d)灌胃,第9天处死各组大鼠。免疫组化法检测各组肾组织CTGF、转换生长因子β1(TGF-β1)和α-平滑肌肌动蛋白(α-SMA)的表达;RT-PCR方法检测各组CTGFmRNA含量;Masson染色评定各组肾小管间质损害程度。结果:模型组CTGF、TGF-β1、α-SMA的表达及肾小管间质损伤指数明显高于假手术组(P<0.01),而GPs组和缬沙坦组各项指标明显低于模型组(P<0.01);GPs组与缬沙坦组差异无显著性(P>0.05)。各项指标作相关分析,CTGF与肾小管间质损伤指数(r=0.756,P<0.01)、TGF-β1(r=0.879,P<0.01)、α-SMA(r=0.892,P<0.01)为正相关关系。结论:GPs可以抑制肾纤维化时CTGF表达,从而...     

糖尿病大鼠肾小管上皮细胞-肌成纤维细胞转分化及氯沙坦对其的影响

【目的】观察糖尿病大鼠肾小管上皮细胞-肌成纤维细胞转分化(TEMT)及氯沙坦干预对其的影响。【方法】雄性Wistar大鼠随机分为正常对照组和糖尿病模型组;后者经STZ诱导糖尿病模型成功后再随机分为糖尿病组和氯沙坦干预组[氯沙坦20mg/(kg·d)]。分别于第8周和第16周时每组各处死5只大鼠。测定24h尿蛋白排泄量、血肌酐;留取肾组织作HE和Masson染色,观察肾小管间质损伤指数、肾间质胶原面积;免疫组织化学法检测肾小管上皮细胞α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)和转化生长因子-β1(TGF-β1)表达,并作半定量分析。【结果】①与对照组相比,糖尿病模型组大鼠肾小管间质损伤指数和肾间质胶原面积明显增加(P<0.01);②糖尿病组大鼠肾小管上皮细胞α-SMA、Vimentin和TGF-β1阳性表达均显著高于对照组,α-SMA表达和TGF-β1表达呈正相关(rs=0.810,P<0.01)。③氯沙坦组尿蛋白排泄量、肾小管间质损伤和间质纤维化程度较糖尿病组减轻,肾小管上皮细胞α-SMA、Vimentin与TGF-β1表达强度较糖尿病组显著下调(P<0.01)。【结论】①糖尿病大鼠肾脏病理进程中存在TEMT;②氯沙坦可下调糖尿病大鼠肾小管上皮细胞TGF-β1、Vimentin、α-SMA表达,阻抑糖尿病肾小管上皮细胞发生TEMT而发挥肾脏保护作用。     

缬沙坦对心肌缺血坏死后心肌转化生长因子-β1及ⅠⅢ型胶原表达的影响

目的本研究通过观察缬沙坦对大鼠急性缺血坏死后的心肌转化生长因子-β1(TGF-β1)及Ⅰ、Ⅲ型胶原表达的影响,探讨缬沙坦对心肌缺血坏死后心室重构的作用.方法实验动物随机分为Val组(缺血加缬沙坦组)、MI组(心肌缺血组)和C组(对照组).14 d后将三组动物处死,心肌组织经HE染色作形态学观察,用免疫组化SP法检测心肌组织切片内的TGF-β1及Ⅰ、Ⅲ型胶原表达.结果心肌组织HE染色:Val组和MI组可见心肌纤维溶解断裂、炎症细胞浸润等改变;免疫组化染色结果:Val组与MI组比较,TGF-β1及Ⅰ、Ⅲ型胶原表达量明显降低(P＜0.01).结论缬沙坦可明显降低心肌缺血坏死后心肌Ⅰ、Ⅲ型胶原和TGF-β1的表达,从而减轻了心室的重构.     

自拟地龙活血汤对阿霉素肾硬化影响的实验研究

[目的]探讨自拟地龙活血汤对肾小球硬化模型大鼠的治疗效果.[方法]复制阿霉素肾硬化模型,用自拟地龙活血汤进行干预, 观测各组大鼠在做模型前、药物干预后的尿蛋白、尿糖、血浆白蛋白(ALB)、尿素氮(BUN)、肌酐(Cr)、血脂(TG、CHO)的变化.并在用药干预2个月后,观察肾脏组织中肾小球硬化和其他病理损伤程度;免疫组化SABC法检测肾组织Ⅲ型胶原(Collagen Ⅲ)、Ⅳ型胶原(Collagen Ⅳ)、转化生长因子-β1(TGF-β1).[结果]肾硬化组出现严重的蛋白尿,肾功能严重损伤(BUN、Cr升高显著);肾硬化组大鼠肾小球系膜基质增生、系膜区增宽、基底膜断裂、肾小球与肾小囊粘连、大量肾小球局灶硬化,肾小球周围纤维化明显、炎性细胞重度浸润.药物治疗组的蛋白尿、肾功能和病理改变较肾硬化组有明显的改善,在肾小球硬化、肾小管损伤改变上较硬化组明显减轻(P＜0.01).肾组织内Ⅲ型、Ⅳ型胶原和TGF-β1蛋白表达水平药物治疗组较肾硬化组有明显的减轻.[结论]地龙活血汤能明显改善大鼠的临床症状、肾功能,减少肾小球ECM成分的积聚;其减少肾小球ECM积聚的可能机制是通过干预TGF-β1而实现的,最终延缓肾小球硬化.     

曲尼司特对环孢素A慢性肾毒性大鼠肾脏TGF-β1、Ang Ⅱ及col Ⅲ的影响

目的:探讨曲尼司特(tranilast,TNL)对环孢素A(CsA)慢性肾毒性大鼠血清及肾脏血管紧张素Ⅱ(AngⅡ)及肾脏转化生长因子-β1(TGF-β1)、Ⅲ型胶原(ColⅢ)的影响。方法:雄性SD大鼠24只,随机分成正常对照组、模型组、TNL治疗组、安博维治疗组。采用低盐饮食加CsA 20 mg/(kg.d)灌胃的方法建立CsA慢性肾毒性肾脏模型。观察TNL对大鼠肾脏病理及肾组织Ang Ⅱ、TGF-β1、ColⅢ的影响。结果:TNL能下调CsA慢性肾毒性大鼠血清及肾组织中AngⅡ的水平及肾组织TGF-β1、ColⅢ在肾脏的表达。结论:TNL可能通过抑制AngⅡ、TGFβ1及ColⅢ的表达而发挥其抗纤维化作用。     

抗纤灵对5/6肾切除大鼠肾组织α-SMA和Ⅰ型胶原的影响

目的采用5/6肾切除方法建立慢性肾衰竭动物模型,观察抗纤灵对5/6肾切除大鼠肾组织α-SMA和Ⅰ型胶原的影响。方法将SD大鼠随机分为假手术组和造模组,造模组以5/6肾切除方法建立慢性肾衰竭动物模型,1周后按血肌酐水平将造模大鼠分为模型组、福辛普利组和抗纤灵组。福辛普利组给予3.3mg.kg-1.d-1福辛普利灌胃,抗纤灵组给予23g.kg-1.d-1抗纤灵灌胃,模型组和假手术组给予等量生理盐水灌胃,8周后采用免疫组化、实时荧光定量PCR(RT-PCR)和蛋白免疫印迹法(Westernblot)测定各组大鼠肾组织α-SMA和Ⅰ型胶原基因和蛋白的表达。结果模型组大鼠肾组织中肾小管及间质区Ⅰ型胶原及α-SMA表达较假手术组明显升高(P<0.01),抗纤灵组与模型组比较均明显下降(P<0.01);模型组大鼠表达α-SMAmRNA和Ⅰ型胶原mRNA水平较假手术组明显升高(P<0.001),抗纤灵组与模型组比较均明显下降(P<0.01或P<0.05);模型组大鼠表达α-SMA和Ⅰ型胶原蛋白水平较假手术组明显升高(P<0.001),抗纤灵组与模型组比较均显著下降(P<0.001)。结论抗纤灵可降低肾间质成纤维细胞α-SMA的表达,减少肌成纤维细胞的活化与形成,继而使细胞外基质Ⅰ型胶原生成减少,从而延缓慢性肾衰竭大鼠肾纤维化进程,保护残肾功能。     

冬虫夏草对糖尿病大鼠肾小管上皮细胞ILK表达的影响

[目的]观察糖尿病大鼠肾小管上皮细胞整合素连接激酶(ILK)的表达及冬虫夏草对其表达的影响.[方法]雄性Wistar大鼠随机分为3组:正常对照组(N组,n=12)、糖尿病模型组(D组,n=12)、糖尿病冬虫夏草干预组[C组,n=12,冬虫夏草1000 mg/(kg·d)灌胃].成模后第8周末及16周末各组分别处死6只大鼠,测定24 h尿蛋白排泄量、血肌酐;HE及MASSON染色法观察肾脏病理改变;免疫组织化学法检测ILK、E钙粘蛋白(E-cad)、α平滑肌肌动蛋白(α-SMA)及转化生长因子β1(TGF-β1)的表达.[结果]①与N组比较,D组大鼠肾小管间质损伤指数、肾间质胶原面积明显增加(P<0.01).②D组大鼠肾小管上皮细胞E-cad阳性表达显著低于N组,TGF-β1、ILK和α-SMA阳性表达均显著高于N组;E-cad表达和TGF-β1表达呈负相关(rs=-0.60,P<0.05);ILK、α-SMA表达和TGF-β1表达呈正相关(rs=0.88,P<0.01;rs=0.91,P<0.05).③C组大鼠肾小管间质损伤指数、肾闻质胶原面积较D组明显减弱,其肾小管上皮细胞的E-cad的表达较D组明显增加,TGF-β1、ILK和α-SMA表达较D组均明显减弱(P<0.01).[结论]冬虫夏草能通过下调ILK表达发挥肾脏保护作用.     

组织型转谷氨酰胺酶与转化生长因子β1在幼鼠肾间质损伤中的表达及意义

目的探讨组织型转谷氨酰胺酶(tTG)和转化生长因子β1(TGF-β1)在幼鼠肾间质损伤中的表达及意义。方法清洁级雄性Wistar幼年大鼠60只,采用随机数字表法分为假手术组、模型组和试验组,每组20只。模型组和试验组幼鼠建立单侧输尿管结扎模型,试验组从建模后第2天起灌胃给予苯那普利和氯沙坦各6mg/(kg·d),1次/天。于造模后第3、7、14、28天,分别处死5只大鼠,取肾组织,采用Masson染色检测肾组织常规病理变化,采用RT-PCR法检测tTG和TGF-β1mRNA表达水平。结果造模后第3、7、14、28天,模型组和试验组肾间质纤维组织相对面积明显高于假手术组,差异有统计学意义(P0.05),且试验组明显低于模型组,差异有统计学意义(P0.05)。造模后第3、7、14、28天,模型组和试验组tTG和TGF-β1mRNA均明显高于假手术组,差异有统计学意义(P0.05),且试验组明显低于模型组,差异有统计学意义(P0.05)。tTG与TGF-β1和肾间质纤维组织相对面积呈正相关关系,TGF-β1与肾间质纤维组织相对面积呈正相关关系。结论 tTG和TGF-β1互相作用参与肾间质纤维化过程,苯那普利可能通过调节tTG和TGF-β1表达水平实现其肾保护作用。tTG和TGF-β1具有成为肾间质纤维化治疗的潜在有效靶点。     

血管紧张素Ⅱ受体阻断剂对慢性肾脏病患者肾素-血管紧张素系统表达的影响

目的：研究血管紧张素Ⅱ受体阻断剂（angiotensinⅡ receptor blocker,ARB）对慢性肾脏病（chronic kidney disease,CKD）患者循环和肾脏肾素-血管紧张素系统（renin-angiotensin system,RAS）表达的影响。方法：行肾脏活组织检查且2个月内未曾服用血管紧张素转换酶抑制剂的CKD患者,其中2周内ARB治疗的患者17例（ARB治疗组）,另选取2周内未应用ARB治疗的患者17例（空白对照组）,根据年龄、性别、血压、估算肾小球滤过率（eGFR）、24h尿蛋白、尿钠等进行配对。采用放射免疫法和酶联免疫吸附分析（ELISA）方法测定血、尿RAS组分的浓度,并采用免疫组织化学方法评价肾脏肾素、血管紧张素原（AGT）、血管紧张素Ⅱ（AngⅡ）和血管紧张素Ⅱ受体的表达。分析ARB对血、尿和肾组织RAS表达的影响。结果：ARB治疗组与空白对照组在性别、年龄、eGFR、24h尿蛋白、尿钠和血压等方面均显著差异。ARB治疗组血浆AngⅡ高于空白对照组[（63.09±15.14）pg/mL比（53.66±8.33）pg/mL,P〈0.05],肾内肾素免疫组织化学染色面积高于空白对照组[（48.65±19.58）%比（30.29±24.98）%,P〈0.05]。ARB治疗组肾内AGT、AngⅡ和血管紧张素Ⅱ1型受体免疫组织化学染色面积略低于空白对照组,但差异无统计学意义。结论：ARB治疗对循环和肾脏局部RAS表达的影响不同,可使循环AngⅡ升高,并可能抑制肾脏局部AngⅡ的表达。     

Uric Acid in Human Plasma III. Investigations on the Interaction Between the Urate Ion and Human Albumin

Kosunen, K. J. A Simple Method for Measurement of Angiotensin II in Plasma. Scand. J. clin. Lab. Invest. 36, 467–472, 1976.

A simple radioirrtmunological (RIA) method for the determination of angiotensin II in 0.5–1.0 ml samples of plasma is described and carefully evaluated. Before RIA was performed, the interfering plasma proteins were eliminated by ion exchange chromatography, and recovery from every column was checked with a small amount of [¹²⁵I]angiotensin II. The sensitivity of the method was 4.0 ng/1; the coefficient of intra-assay variation was 10.0% and that of inter-assay variation 12.1%. Accuracy was studied both by adding various amounts of angiotensin II to plasma samples and by diluting plasma containing angiotensin II with the RIA buffer. Both studies gave very good correlations between found and expected values (r=0.998 and r=0.987). In a normal material (n=36), the mean angiotensin II concentration at 8 a.m. after a night's bed rest was 31.1 ±10.7 (S.D.) ng/1 and at 10 a.m. after 2 h ambulation 42.4±12.8 (S.D.) ng/1. Because the present method is accurate, precise, and practical, and allows measurement of angiotensin II in small samples, it seems useful for routine as well as for research work.     

自发性高血压大鼠心脏和肾脏血管紧张素转换酶2和血管紧张素转换酶的表达

目的 观察不同月龄的自发性高血压大鼠(SHR)的心脏和肾脏血管紧张素转换酶2(ACE2)和血管紧张素转换酶(ACE)的Mrna和蛋白质表达水平,探讨ACE2/ACE与血压状态的内在联系.方法 12周龄雄性自发性高血压大鼠(spontaneously hypertensive rat,SHR)18只和12周龄WKY大鼠(Wistar-Kyoto rats,WKY)18只.随机分为SHR组和WKY组,每组抽取各9只,处死进行与喂养12周后处死的24周龄大鼠相同的研究内容.采用实时定量RT-PCR法(Real-time Quantitative RT-PCR)检测ACE2、ACE Mrna(messenger ribonucleic acid,Mrna)的表达,免疫组织化学榆测ACE2、ACE等蛋白的表达.结果 (1)与同周龄WKY组比较,SHR组的血压显著增加(P均＜0.01),心脏和肾脏的ACE2 Mrna表达显著降低(P均＜0.01),ACEmRNA表达显著升高(P＜0.05,P＜0.01);与12周龄SHR组比较,24周龄SHR的血压亦显著增加(P＜0.01),ACE2 Mrna表达显著降低(P均＜0.01),ACE Mrna表达显著升高(P均＜0.01).(2)与同周龄的WKY组比较,SHR组心脏和肾脏的ACE2免疫染色表达显著减少,ACE免疫染色表达显著增多.结论 心脏和肾脏的ACE2/ACE Mrna表达与血压升高相关.     

Effect of indomethacin upon angiotensin-induced changes in blood pressure and plasma aldosterone in normal man

Abstract. The effect of indomethacin (75 mg/day for 3 days) on the response to i.v. angiotensin II was investigated in eight healthy, sodium-repleted, male subjects. Indomethacin reduced the release of aldosterone during the i.v. administration of angiotensin II (5, 10 and 20 ng kg^-1 min^-1), whereas the pressor response to angiotensin II and to succinamyl¹-val⁵-phenylglycine-acetate⁸-angiotensin II, an agonistic angiotensin II-analogue, was increased. Plasma renin concentration was reduced following treatment with indomethacin. These data confirm the modulatory influence of endogenous prostaglandins upon the vasoconstrictor effect of angiotensin II and could suggest a direct interference of prostaglandins with the secretion of aldosterone.     

子痫前期患者外周血中抗血管紧张素Ⅱ受体1型自身抗体的表达

目的 通过检测抗血管紧张素Ⅱ受体1型自身抗体(AT1-AA)在子痫前期患者外周血中的表达,探讨其在子痫前期发病中的病理生理机制.方法 选择子痫前期患者30例,正常晚期妊娠患者20例,未孕健康妇女20例.以合成的抗血管紧张素Ⅱ受体为抗原,采用间接SA-ELISA法检测外周血AT1-AA的表达.结果 子痫前期组外周血AT1-AA的阳性率为(65.0±4.7)%,明显高于正常晚期妊娠对照组(26.0±2.8)%和未孕健康妇女对照组(7.8±2.2)%,差异均有统计学意义(t值分别为24.97、38.56,P均＜0.01).正常晚期妊娠对照组的阳性率与未孕健康妇女对照组比较差异也有统计学意义(t=4.58,P＜0.05).结论 子痫前期患者外周血中的抗AT 1-AA高于正常孕妇和未孕健康妇女,提示AT1-AA在子痫前期发病中其重要作用;正常孕妇血清中抗AT1-AA的阳性率也明显高于同龄未孕健康妇女,提示孕期有免疫机制的参与.

Abstract：

Objective To investigate the role of subtype 1 autoantibody against angiotensin Ⅱ receptor in the pathogenesis of preeclampsia by detecting its expression in the peripheral blood of preeclampsia patients,Methods Thirty patients with preeclampsia were assigned to preeclampsia group. Twenty normal pregnant women at the late stage and twenty non-pregnant healthy women as controls were investigated. The level of type 1 antoantibody against angiotensin Ⅱ in the peripheral blood was detected by indirect SA-ELISA assay with the produced ATR-1 as the antigen. Results The level of subtype 1 antoantibody against angiotensin Ⅱ (65 ±4. 7) % in the peripheral blood of preeclampsia patients is significantly higher than that of normal late pregnant (26 ±2. 8)% and non-pregnant women(7.8 ±2. 2)% groups (t1 =24. 97 ;t2 =38.56;P ＜0. 01 for both) ;The angiotensin Ⅱ receptor subtype 1 autoantibody in the group of normal late pregnancy (26 ± 2. 8 )% was significantly higher than that of healthy non-pregnant women group ( 7. 8 ± 2. 2 ) % ( t = 4. 58, P ＜ 0. 05 ).Conclusion Compared with the normal pregnant women and the healthy non-pregant women, the autoantibody against AT1 receptor in sera of preeclamptic patients is elevated ata high frequency. These results suggest that overproduction of AT1-AA may play an important role during the development of preeclamptic patients. AT1-AA is a novel risk factor in pregnant women. Immune mechanisms may be involved in the process of pregnancy.     

Endothelium-derived vasoactive agents, AT1 receptors and inflammation

Angiotensin II, through activation of the angiotensin II-type 1 receptor, induces generation of inflammatory mediators in the blood vessel wall and as such plays an active role in the inflammation process. Direct stimulation of reactive oxygen species and nuclear factors seem to be key mechanisms through which this receptor induces inflammation. Inflammatory molecules are also known to modify endothelial cell function, especially endothelium-derived vasoactive agents, and inflammation is increasingly recognized as primary cause of major vascular disorders. There is accumulating evidence that stimulation of the type 1 angiotensin II receptor participates in vascular dysfunction by reducing activity of the endothelium-derived relaxants nitric oxide and hyperpolarizing factors. Furthermore activation of this angiotensin II receptor also enhances generation of endothelium-derived constricting factors, such as endothelin-1. This change in endothelial cell output not only impairs blood vessel relaxation but leads to pro-inflammatory and pro-coagulation conditions that are associated with disease initiation and progression. Pharmacological inhibitors of the angiotensin II pathway and the type 1 receptor subtype are in current clinical use for the treatment of hypertension. However evidence supports that these agents have a positive therapeutic benefit in other vascular pathologies with recognized inflammatory etiology, such as atherosclerosis.     

The mechanism of action of angiotensin II is dependent on direct activation of vascular smooth muscle carbonic anhydrase I

Our previous studies have shown that angiotensin II increases carbonic anhydrase activity both in vitro and in vivo. In this study we investigated in vitro the effect of angiotensin II on carbonic anhydrase I and II from erythrocytes and on arteriolar vascular smooth muscle carbonic anhydrase I. We also studied in vitro and in vivo the effect of angiotensin II receptor blockers (irbesartan and candesartan) on purified carbonic anhydrase I and II, on vascular smooth muscle carbonic anhydrase I and on arterial blood pressure in humans and in animals. In vitro results showed that angiotensin II is a direct and stronger activator of carbonic anhydrase I than II. Angiotensin II receptor blockers reduced mainly carbonic anhydrase I activity and completely antagonized the activating effect of angiotensin II both on purified and on vascular smooth muscle carbonic anhydrase I. Our in vivo experiments showed that irbesartan and candesartan are powerful inhibitors of carbonic anhydrase I both in erythrocytes (in humans) and in vascular smooth muscles (in animals). In humans, irbesartan and candesartan progressively reduce arterial blood pressure in hypertensive subjects, in parallel with progressive reduction of erythrocyte carbonic anhydrase I activity. We believe that angiotensin II could have a dual mechanism of action: (1) angiotensin interacting with its receptor to form a stimulus-receptor complex; (2) the same stimulus directly acts on the carbonic anhydrase I isozyme (which might be coupled with angiotensin II receptors), ensuring an adequate pH for stimulus-receptor coupling for signal transmission into the cell and hence vasoconstriction.     

Role of bone marrow renin-angiotensin system in the pathogenesis of atherosclerosis

The renin–angiotensin system (RAS) has been considered to be a circulating hormonal system that regulates blood pressure, blood flow, fluid volume and electrolyte balance. A growing body of evidence indicates local effects of an activated RAS, particularly in the cardiac, vascular, and renal systems. It is now well established that RAS, especially angiotensin II (Ang II) and Ang II type 1 receptor (AT1R) pathway, has significant pro-inflammatory actions on the vessel wall, leading to progression of atherosclerosis. Recent reports suggest that an activated RAS has local effects in bone marrow (BM), which contributes to the regulation of normal and malignant hematologic processes. We reported that AT1aR in BM cells participate in the pathogenesis of atherosclerosis by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1aR. These results suggest that blockade of AT1R not only in vascular cells but also in BM could be an important strategy to prevent atherosclerosis. In this review, we overview recent findings on a role of RAS in the pathogenesis of atherosclerosis, and discuss functional contribution of a local RAS in BM to progression and destabilization of atherosclerotic plaque.     

Reduced angiogenesis and delay in wound healing in angiotensin II type 1a receptor-deficient mice

Angiotensin II (Ang II) is a bioactive peptide that plays important roles in blood pressure regulation and salt–water homeostasis. Recently, Ang II was reported to function in the promotion of angiogenesis. Since the wound healing process is highly dependent upon angiogenesis, we employed Ang II receptor knockout mice (AT1a^−/−) to investigate whether or not Ang II facilitates angiogenesis and wound healing via AT1a receptor signaling. In comparison to wild-type (WT) mice, wound healing and wound-induced angiogenesis were significantly suppressed in AT1a^−/− mice, and these mice exhibited reduced expression of CD31 in wound granulation tissues. In comparison to vehicle-treated mice, wound healing was delayed significantly in mice treated with an AT1-R antagonist and this delay was accompanied by the reduced expression of vascular endothelial growth factor in wound granulation tissues. These findings suggest that Ang II–AT1a signaling plays a crucial role in wound healing and wound-induced angiogenesis.