不同糖代谢状况对高血压患者心脏结构功能和肾脏功能的影响

目的探讨原发性高性压(EH)患者不同糖代谢状况下心脏结构、功能和肾脏功能的变化。方法312例住院的EH患者,测定空腹血糖(FPG)、肌酐(cr)和尿蛋白肌酐(A/C)比值;其中无糖尿病(DM)病史者,行2h葡萄糖耐量(OGTT)试验。将患者分为OGTT正常(NGT)组、糖调节受损(IGR)组和DM组。54例无EH和DM且OGTT正常者为对照组。采用简化MDRD公式计算肾小球滤过率(eGFR)并评价慢性。肾脏病(CKD),根据A/C比确定微量白蛋白尿(MAU);超声心动图测量左房内径(LAD)、左室舒张末期内径(LVDd)、室间隔厚度(IVST)、左室后壁厚度(LVPW)和左室射血分数(LVEF),计算左室重量指数(INWI)。结果 EH患者合并糖代谢异常比例为80.1%;与对照组比较,3组EH患者随糖代谢状况恶化,心脏超声指标在正常对照组、EH组中NGT、IGR和DM组分别为LVDd[45.20(5.10)mm、45.80(3.00)mm、47.05(5.28)mm、47.50(5.80)mm,P<0.01]和LVWI[(83.75±1.14)g/m~2、(93.11±1.36)g/m~2、(101.37±1.27)g/m~2、(106.61±1.43)g/m~2,P<0.05或0.01],EF值[60.4(6.5)%、61.1(7.6)%、57.7(8.6)%、56.9(7.3)%,P<0.01]和eGFR水平[(82.77±21.13)ml·min~(-1)·1.73 m~(-2)、(69.86±13.75)ml·min~(-1)·1.73 m~(-2)、(63.83±15.51)ml·min~(-1)·1.73 m~(-2)、(58.56±18.28)ml·min~(-1)·1.73 m~(-2),P<0.01]下降,MAU(2.4%、9.6%、25.0%、41.2%,P<0.05或0.01)和CKD比例(10.9%、21.0%、41.2%、48.5%,P<0.05或0.01)增加。结论高血压患者糖代谢异常发生率较高,合并IGR和DM可加重心脏结构、功能和肾脏功能损害,对既往无DM病史EH患者,OGTY应作为一项常规检查。     

胰激肽原酶对自发性高血压大鼠肾脏结构与功能的保护作用

目的:观察胰激肽原酶干预对自发性高血压大鼠(SHR)肾脏结构与功能的影响,探讨激肽释放酶-激肽系统在高血压及肾脏保护方面的作用。方法:12只36周龄SPF级雄性SHR随机分成2组,治疗组给予胰激肽原酶(800U/kg/d)灌胃治疗12周,观察大鼠血压、血肌酐(Scr)、尿素氮(BUN)及尿微量白蛋白(mALB)、尿β2微球蛋白(β2-MG)、N-乙酰-β-D-氨基葡萄糖苷酶(NAG)浓度及肾脏组织病理改变,并用逆转录-聚合酶链反应(RT-PCR)方法测定肾皮质组织型激肽释放酶 mRNA的表达。结果:较之SHR对照组胰激肽原酶治疗后血压明显下降(P<0.01);尿mALB、β2-MG、NAG定量明显降低(P<0.01);肾皮质组织型激肽释放酶 mRNA表达水平增加(P<0.05)。病理上SHR对照组大鼠肾小球小动脉管壁增厚,管腔狭窄,个别小球硬化;胰激肽原酶治疗组肾小动脉结构正常,未见肾动脉硬化。结论:胰激肽原酶能显著减少尿微量蛋白、逆转肾小动脉硬化改变,保护肾功能,其机制可能与降低血压,增加肾脏中组织激肽释放酶水平有关。     

依那普利和氯沙坦对自发性高血压大鼠肾脏环核苷酸水平的影响

1　资料与方法14周龄雄性自发性高血压大鼠 (SHR) 18只 ,相同周龄的雄性大鼠WKY6只。共分 4组 ,WKY对照组以等量蒸馏水灌胃 ,SHR随机分为依那普利组、氯沙坦组、SHR对照组 3组 ,分别以依那普利 (15mg·kg- 1 ·d- 1 )、氯沙坦 (37.5mg·kg- 1 ·d- 1 )、等量蒸馏水灌胃。各组均灌胃 2周。环磷酸腺苷(cAMP)、环磷酸乌苷 (cGMP)放射免疫药盒由上海中医药大学同位素室提供 ,血管紧张素Ⅱ (AngⅡ )放射免疫药盒购自北京福瑞生物工程公司。硝酸盐 (NO3- )浓度测定采用北京东亚免疫技术研究所提供的NO2- 测定试剂盒 ,用Griess法检测一…     

通心络对自发性高血压大鼠阻力血管功能和结构的影响

目的观察通心络对自发性高血压大鼠(SHR)的血压、阻力血管功能和结构的影响.方法 30只12周龄雄性SHR大鼠,随机分成3组:大剂量通心络组(通心络1.5 g/kg*d-1);小剂量通心络组(通心络0.5 g/kg*d-1);SHR空白对照组,每组10只.另选10只同龄雄性正常血压WKY大鼠作为对照组.用无创法测定尾动脉收缩压及心率,至给药12周处死.测定肠系膜动脉分支第三级血管壁(中膜)/腔面积比(W/L).采用平衡记录仪记录离体的肠系膜一级动脉环对血管活性药物去甲肾上腺素和硝普钠反应的敏感性.结果与SHR组相比,大小剂量通心络组均能在一定程度上抑制SHR血压升高(P<0.05).通心络组治疗后能使SHR大鼠的肠系膜三级血管的血管腔/壁面积比(L/W)减少,肠系膜动脉舒张敏感性及对NE收缩的敏感性与SHR组相比P<0.05.结论通心络可以抑制SHR阻力血管肥厚,具有改善血管的舒缩功能.     

硝苯地平和贝那普利对高血压患者肾脏功能的影响

目的探讨硝苯地平和贝那普利对高血压患者肾脏功能的影响。方法将90例高血压患者随机分成硝苯地平组、贝那普利组和联合治疗组各30例,硝苯地平组给予30 mg/d硝苯地平控释片口服,贝那普利组给予10 mg/d贝那普利片口服,联合治疗组给予30 mg/d硝苯地平控释片+10 mg/d贝那普利片口服,连续治疗12周。测定患者治疗前和治疗6周、12周末时的血压,24 h尿白蛋白、β2-微球蛋白(β2-MG)含量以及外周血中尿素氮(BUN)、肌酐(SCr)水平。结果三组治疗后血压、SCr和BUN水平均显著降低(P均<0.05),但组间降压幅度无统计学差异(P>0.05)。24 h尿白蛋白和β2-MG均较治疗前显著降低,且联合治疗组较单药组下降幅度更明显(P均<0.05)。结论硝苯地平和贝那普利单独用于治疗高血压可减少尿白蛋白水平,保护肾脏功能,两药联合效果更佳。     

氟伐他汀对自发性高血压大鼠阻力血管结构和功能的影响

目的 探讨氟伐他汀对自发性高血压大鼠（ＳＨＲ）阻力血管结构和功能的影响。方法 ＳＨＲ大鼠出生后８周给予氟伐他汀２０ｍｇ．ｋｇ＾－１．ｄ＾－１。应用计算机图象分析,计算血管壁腔比,观察三组大鼠肠系膜动一级分支及主动脉结构变化,采用离体的主动脉和肠系膜动脉环在管活性药物：去甲肾上腺素和硝普钠反应的敏感性,观察治疗后血管的功能变化。结果 治疗８周后,氟伐他汀组（ＳＨＲｆｌｕ）收缩压比对照组（ＳＨＲ）平均     

复合离子盐对高血压大鼠肾脏功能及结构的影响

目的研究复合离子盐对自发性高血压大鼠(SHR)肾脏功能及结构的影响,并探讨其可能的机制.方法 38只8周龄雄性SHR随机分为4组:8%食盐摄入组(HS group);1%复合离子盐摄入组(CIS group);1%复合离子盐 2.25% L-Arg摄入组(CIS L-Arg group);1%食盐摄入组(NS group),持续干预12周.干预期间定期观察大鼠体重、血压、尿量、尿钠及尿蛋白的变化.12周末进行有创血压测量,放射免疫法检测肾皮质中Ang Ⅱ、NO含量.进行肾脏组织HE及天狼猩红染色,观察病理变化并计算胶原容积分数.结果 12周干预结束后,CIS组与CIS L-Arg组血压升高趋势明显低于NS组.CIS组与CIS L-Arg组尿蛋白在干预期间没有发生明显改变,且较NS组低.与NS组相比,CIS组与CIS L-Arg组SHR肾小球及肾小管周胶原沉积量少,肾脏损害较轻,肾皮质Ang Ⅱ含量较低,NO含量较高;HS组SHR肾小球及肾小管周则胶原沉积明显增多,肾脏损害较重,肾皮质Ang Ⅱ含量较高,而NO含量较低(all P＜0.01).结论复合离子盐与普通食盐比较,长期同等量摄入时可改变肾皮质中Ang Ⅱ、NO含量,改善肾功能,延缓SHR血压的升高,减轻肾脏功能结构损害,L-Arg的加入可能有协同复合离子盐的作用.     

复合离子盐对高血压大鼠肾脏功能及结构的影响

目的研究复合离子盐对自发性高血压大鼠(SHR)肾脏功能及结构的影响,并探讨其可能的机制。方法38只8周龄雄性SHR随机分为4组:8%食盐摄入组(HSgroup);1%复合离子盐摄入组(CISgroup);1%复合离子盐 2·25%L-Arg摄入组(CIS L-Arggroup);1%食盐摄入组(NSgroup),持续干预12周。干预期间定期观察大鼠体重、血压、尿量、尿钠及尿蛋白的变化。12周末进行有创血压测量,放射免疫法检测肾皮质中AngⅡ、NO含量。进行肾脏组织HE及天狼猩红染色,观察病理变化并计算胶原容积分数。结果12周干预结束后,CIS组与CIS L-Arg组血压升高趋势明显低于NS组。CIS组与CIS L-Arg组尿蛋白在干预期间没有发生明显改变,且较NS组低。与NS组相比,CIS组与CIS L-Arg组SHR肾小球及肾小管周胶原沉积量少,肾脏损害较轻,肾皮质AngⅡ含量较低,NO含量较高;HS组SHR肾小球及肾小管周则胶原沉积明显增多,肾脏损害较重,肾皮质AngⅡ含量较高,而NO含量较低(allP<0·01)。结论复合离子盐与普通食盐比较,长期同等量摄入时可改变肾皮质中AngⅡ、NO含量,改善肾功能,延缓SHR血压的升高,减轻肾脏功能结构损害,L-Arg的加入可能有协同复合离子盐的作用。     

非洛地平治疗老年人单纯收缩期高血压的疗效观察及对肾脏功能的影响

钙拮抗剂作为重要的抗高血压药物，一直为临床广泛使用。非洛地平是一种新型的二氢吡啶类钙离子拮抗剂，由于降压平稳和长效，特别适合老年高血压的治疗。我们通过４～６ｗ用药前后２４ｈ动态血压监测（ＡＢＰＭ）和自身用药前后β２微球蛋白（β２－ＭＧ）变化，观察了非...     

抑郁对自发性高血压大鼠水通道蛋白-2的影响

目的探讨抑郁对自发性高血压大鼠水通道蛋白2（aquaporin2,AQP2）的影响,并探讨AQP2在高血压中的病理生理作用。方法60只SHR大鼠分为对照组（n=30）和抑郁组（n=30）,两组又各分为两个亚组：对照组非药物治疗亚组（n=15）、对照组贝那普利治疗亚组（n=15）;抑郁组非药物治疗亚组（n=15）、抑郁组贝那普利治疗亚组（n=15）。另外,选取Wistar Kyoto（WKY）大鼠20只作为正常组大鼠。药物治疗亚组大鼠予贝那普利10 mg.d-1.kg-1灌胃。抑郁组大鼠采用慢性不可预计温和应激（CUMS）结合行为学指标建立自发性高血压大鼠并抑郁动物模型。对照组、正常组大鼠动物正常饲养。检测并比较各组大鼠间血压的变化及血管加压素和肾脏AQP2表达的差异。结果 （1）抑郁组非药物治疗亚组血压（175±14）mm Hg高于对照组非药物治疗亚组（160±11）mm Hg及正常组（112±9）mm Hg,差异有统计学意义（P〈0.05）;贝那普利治疗后,抑郁组治疗亚组血压（136±15）mm Hg、对照组治疗亚组（113±12）mm Hg均低于各自非药物治疗组（P〈0.05）。（2）抑郁组非药物治疗亚组与正常组、对照组非药物治疗亚组及对照组贝那普利治疗亚组比较,糖水偏爱性均减低（P〈0.05）,体质量和旷场实验评分均明显下降（P〈0.05）,血浆血管加压素浓度升高[（9.31±0.42）pg/mL vs.（1.6±0.67）pg/mL、（3.04±0.97）pg/mL、（2.34±0.91）pg/mL,P〈0.05],AQP2蛋白表达增加（0.95±0.12 vs.0.12±0.07、0.44±0.06、0.24±0.06,P〈0.05）。（3）抑郁组贝那普利治疗亚组与对照组非药物治疗亚组、对照组贝那普利治疗亚组比较,糖水偏爱性均减低（P〈0.05）,体质量和旷场实验评分均明显下降（P〈0.05）,血浆血管加压素浓度升高[（4.55±0.69）pg/mL vs.（3.04±0.97）pg/mL、（2.34±0.91）pg/mL,P〈0.05],AQP2蛋白表达增加（0.62±0.17 vs.0.12±0.07、0.44±0.06,P〈0.05）。（4）对照组贝那普利治疗亚组与抑郁组非药物治疗亚组比较,糖水偏爱性亦增加（P〈0.05）,体质量和旷场实验评分升高（P〈0.05）,血浆AVP浓度下降[（4.55±0.69）pg/mL vs.（9.31±0.42）pg/mL,P〈0.05],AQP2蛋白表达减少（0.62±0.17 vs.0.95±0.12,P〈0.05）。结论抑郁可以促进自发性高血压大鼠血管加压素的分泌及肾脏AQP2的表达。抑郁可能通过促进血管加压素的分泌及肾脏AQP2的表达影响高血压的发展。     

盐酸埃他卡林对脑卒中易感型自发性高血压大鼠心功能的影响

目的研究盐酸埃他卡林（Ipt）对大鼠无创心功能参数的影响。方法利用清醒无创心功能血流动力学计算机监测系统,对比研究Ipt对正常血压大鼠和脑卒中易感型自发性高血压大鼠（SHRsp）心率、心脏收缩、舒张和泵血功能的影响。结果Ipt0.5mg/kg静注可降低SHRsp心率、室缩波、抑制心肌收缩力指数,延长左室射血期和心肌电机械收缩时间,降低心输出量,延长左室舒张期。Ipt相同剂量对正常血压大鼠心功能参数却无明显影响。结论Ipt可抑制SHRsp大鼠心脏收缩和泵血功能,延长左室舒张期时间,但不影响正常血压大鼠心脏功能,提示Ipt对心功能的影响与血压状态密切相关。     

Renovascular hypertension: Effects of mesenchymal stem cells in the contralateral hypertensive kidney in rats

Mesenchymal stem cells (MSC) induced neovascularization and improved renal morphology of the stenotic kidney in 2 kidneys-1 clip (2K-1C) model of renovascular hypertension. The present study evaluated the effects of MSC in the contralateral hypertensive kidney. Three weeks after left renal artery occlusion, MSC were injected into the tail vein of the 2K-1C rats. Renal function and morphology were analyzed in both kidneys. Labeled MSC were found in stenotic and contralateral kidneys. Hypertensive 2K-1C animals presented increased circulating levels of Angiotensin II (Ang II) and renin. MSC prevented the progressive increase of blood pressure and reduced circulating Ang II and renin levels. Stenotic kidney showed reduced renal plasma flow (RPF) and glomerular filtration rate (GFR), whereas the contralateral kidney had a tendency (p > 0.5) of reduction in GFR in spite of unchanged RPF. MSC treatment caused an improvement in GFR with no effect of on RPF in the stenotic kidney. Contralateral kidney showed increased diuresis and natriuresis that were even higher in MSC-treated animals, indicating that cell treatment improved the capacity of the contralateral kidney to excrete sodium. Contralateral kidney expressed higher levels of inflammatory cytokines (IL-6, TNF-α) and signs of fibrosis, which were attenuated by MSC treatment. MSC treatment improved the stenotic kidney function, and it was also beneficial to the contralateral hypertensive kidney because it improved the morphology and preserved its capacity to excrete sodium.     

Favorable cardiac and aortic remodeling in olmesartan-treated spontaneously hypertensive rats

Cardiovascular remodeling contributes to the progression of cardiovascular disease. Thus, our aim was to evaluate the action of long-term treatment with olmesartan on cardiac and aortic adverse remodeling and its relationship with blood pressure (BP) and tensile forces acting on the aortic wall. Five-month-old male rats were divided in: WKY group (n = 6), SHR group (n = 6), and SHRs treated with hydralazine 30 mg/kg/day (SHR-H, n = 8) or olmesartan 10 mg/kg/day (SHR-O, n = 8). Medications were administered for 16 weeks. The SHR group showed hypertension (189 ± 4 mmHg), cardiomyocyte hypertrophy (+107%), interstitial fibrosis (5.7% vs 1.9% in WKY), and reduced intramyocardial vascularization (9.1% vs 22.8% in WKY). In aorta, the SHRs showed outward hypertrophic remodeling, increased elastic fibers content (+36%), and increased circumferential wall tension (CWT, 2.79 × 10⁴ dyne/cm) and tensile stress (TS, 261.4 × 10⁴ dyne/cm²). Hydralazine and olmesartan decreased BP (−45% approximately) and likewise CWT and TS (−45% and −35% approximately). Both medications prevented left ventricle remodeling, but olmesartan improved cardiomyocyte hypertrophy better than hydralazine. Hydralazine did not alter media hypertrophy, but it enlarged lumen diameter and increased elastic fibers. It is unlikely that olmesartan prevented all aortic alterations. Taken together, long-term control of BP alone is not sufficient to prevent aortic remodeling due to hypertension, but in myocardium it seems to be enough, except for cardiomyocyte hypertrophy. The differential action of olmesartan suggests that it is essential to block growth stimulation by angiotensin II in cardiomyocytes and vascular smooth muscle cells in order to better prevent cardiovascular adverse remodeling due to arterial hypertension.     

糜酶抑制剂对自发性高血压大鼠心肌纤维化的影响

目的观察心脏糜酶在自发性高血压大鼠（SHR）心肌组织胶原合成和心肌纤维化中的作用。方法应用病理检查、计算机分析结合逆转录-聚合酶链式反应等方法,检测SHR应用糜酶抑制剂组（ChyI组）、SHR组及对照正常血压大鼠WistarKyoto组（WKY组）收缩压、心肌胶原容积分数（CVF）、心肌血管周围胶原面积比（PVCA）和心肌糜酶及I、III型胶原mRNA表达。结果ChyI组心脏CVF、PVCA分别为（27±9）%和0.4±0.1,SHR组分别为（46±8）%和1.9±0.9,WKY组为（24±11）%和0.4±0.1,ChyI组比SHR组显著下降（P<0.01）,与WKY组无显著差异。ChyI组心肌组织I、III型胶原和糜酶mRNA表达相对含量均显著低于SHR组（P<0.01）,与WKY组无显著差异。应用ChyI后大鼠血压与SHR比较,无显著改变。结论心肌组织糜酶参与胶原的合成,参与细胞外基质的形成和降解,促进SHR心肌纤维化,糜酶抑制剂可能对改善心肌纤维化有益。     

Increased expression and activity of phospholipase C in renal arterioles of young spontaneously hypertensive rats

BACKGROUND: The aims of this study were to document the presence of phospholipase C (PLC) isozymes beta(1), gamma(1), and delta(1) in freshly isolated renal glomeruli and resistance vessels, to compare their expression and activity to that in aorta, and to contrast values between 6-week-old Wistar-Kyoto (WKY) controls and 6-week-old spontaneously hypertensive rats (SHR) during the developmental phase of genetic hypertension. METHODS: Aorta, preglomerular arterioles, and glomeruli were isolated from 6-week-old rats using standard techniques. PLC isozyme protein level and activity were determined with Western blot analysis and by measuring inositol 1, 4, 5-trisphosphate (IP(3)) production, respectively. RESULTS: Immunoblots indicate that all three PLC isozymes examined are detectable in freshly isolated preglomerular arterioles, glomeruli, and aorta. Increased levels of PLC-beta(1), and -delta(1) were found in all tested vascular tissues of SHR v WKY. No strain difference was noted for PLC-gamma(1). The relative abundance for both groups was glomeruli > preglomerular arterioles = aorta. The strain difference in protein expression correlated with increased PLC activity in each vascular bed of SHR. CONCLUSIONS: Protein levels of PLC-beta(1) and -delta(1) and PLC activity are upregulated in the systemic and renal vasculature in 6-week-old SHR, suggesting a role in exaggerated vascular reactivity during the development of genetic hypertension. A more complete understanding of the physiologic roles of PLC isozymes and their contributions to specific aspects of cellular function should advance our understanding of vascular tone/reactivity and hypertrophy/remodeling in normal and hypertensive states.     

Effect of Long-Term Losartan Administration on Renal Haemodynamics and Function in Hypertensive Patients

In this study the efficacy and safety of long-term losartan administration on renal haemodynamics were evaluated in mild to moderate hypertension. After a run-in period with placebo, 18 hypertensives without renal or cardiovascular disease were allocated to losartan (50 mg/die for one year) treatment. Renal haemodynamic measurements included renal plasma flow (ERPF) and glomerular filtration rate (GFR) by standardized radioisotope study. Effective renal blood flow (ERBF), filtration fraction (FF), and renal vascular resistance (RVR) were also calculated. Blood pressure was evaluated monthly, whereas renal haemodynamics and function were detected at baseline and after 6 and 12 months of losartan administration. Losartan induced a significant (p < 0.001) decrease in SBP, DBP, and MBP versus baseline values both at 6 months and at 12 months. In addition a significant decrease in RVR (p < 0.001) and in FF (p < 0.05) was also seen. In addition RVR values at 1 year of treatment were higher than their values at 6 months, but this difference was not significant. Our data indicated that long-term control in blood pressure induced by losartan administration was associated with a maintained renal function after 6 months of treatment, but these favourable effects were attenuated after 1 year of treatment.