自发性高血压大鼠肾脏L-精氨酸/一氧化氮系统与红细胞L-精氨酸转运

目的:研究自发性高血压大鼠(SHR)肾脏(L-精氨酸／一氧化氮)L-Arg／NO系统的改变及其与红细胞L-Arg转运的关系。方法:检测16周龄SHR、卡托普利治疗4周的16周龄SHR(CAP)和16周龄WKY大鼠肾脏L-Arg转运、NOS活性、NO₂^-和cGMP含量,红细胞L-Arg转运。结果: SHR肾脏高低亲和L-Arg转运体的Vmax均低于WKY组(P＜0.01,P＜0.05),Km值则无明显差异。NOS活性、NO₂^-、cGMP含量分别较WKY组低35.4%、36.2%和85.2%(P＜0.05或P＜0.01)。CAP组高亲和L-Arg转运体的Vmax、NOS活性均高于SHR组(+90%,P＜0.01;+58.6%,P＜0.05)。NOS活性与高亲和L-Arg转运体的Vmax呈正相关,r=0.585,P＜0.05。红细胞L-Arg转运的改 变与肾脏相似, SHR组的Vmax低于WKY组(－30%,P＜0.01),CAP组高于SHR组(+26.5%,P＜0.01),Km值组间比较无明显差异。红细胞L-Arg转运的Vmax与肾脏高或低亲和L-Arg转运体的Vmax均呈正相关,r=0.8434,P＜0.01(高亲和)和r=0.5255,P＜0.05(低亲和)。 结论:SHR肾脏L-Arg/NO系统活动抑制,卡托普利治疗明显解除此抑制状态。肾脏L-Arg转运的改变与红细胞L-Arg转运的改变基本一致。     

老年男性高血压患者血浆ADM和ET-1含量变化的意义

目的:探讨老年男性高血压患者血浆肾上腺髓质素(ADM)、内皮素-1(ET-1)含量变化的临床意义.方法:用放射免疫分析测定62例老年男性高血压患者血浆ADM、ET-1含量,并与35例年龄、性别匹配的健康老年人对照.结果:高血压组血浆ADM、ET-1含量显著高于正常对照组(P＜0.01),两者均随高血压分级1、2、3级组逐渐递增(P＜0.01,＜0.05);血压控制不良者明显高于血压控制良好者(P＜0.01),病情重组显著高于病情轻组(P＜0.01);伴肾功能受损者也显著高于肾功能正常者(P＜0.01);血浆ET-1含量平均增幅明显高于血浆ADM(P＜0.01);高血压组血浆ADM与ET-1含量呈正相关(r=0.394,P＜0.01);正常对照组两者含量不相关(r=0.172,P＞0.05).结论:老年男性高血压患者血浆舒血管活性肽ADM含量显著增高,可能是机体的一种代偿性自身调节机制,以此抑制ET-1等缩血管活性肽增高对血压调节产生不良的影响,对机体起到自身代偿性保护作用.     

RNA阵列技术检测自发性高血压大鼠肌浆网Ca2+-ATP酶和受磷蛋白基因表达

目的:探讨肌浆网Ca²⁺-ATP酶(SERCA)和受磷蛋白(PLB)在原发性高血压发病过程中的变化特点及其相互关系。方法:提取2、4、6、8、10、12不同周龄雄性自发性高血压大鼠(SHR)和正常血压大鼠(WKY)的心室肌、血管平滑肌、肝脏和肾脏组织的总RNA,共294个样品,利用高通量RNA阵列技术(RNAarray)检测SERCA和PLB基因在不同周龄SHR和WKY中mRNA表达谱改变。结果:SHR在6、8、10、12周龄血压出现显著高于同周龄WKY(均P<0.01),10、12周龄心室肌重量／体重比出现显著增加(均P<0.01),心肌和血管平滑肌SERCA的表达在4、6、8、10、12周龄出现显著高于同周龄WKY(P<0.05或P<0.01)。PLB基因表达在两组间无显著差异(P>0.05)。心肌的SERCA与PLB表达量比值在6、8、10、12周龄出现显著大于同周龄WKY(P<0.05或P<0.01),而血管平滑肌的SERCA与PLB表达量比值在4、6、8、10、12周龄出现显著大于同周龄WKY(P<0.05或P<0.01)。结论:肌浆网SERCAmRNA表达改变及SERCA与PLB比例失常是高血压发生和发展过程中重要的分子生物学机制。     

原发性高血压大鼠降压过程中心钠素和加压素变化的研究

本文研究心得安、异搏定引起原发性高血压大鼠(SHR)降压过程中血浆心钠素(A)和精氨酸加压素(AVP)含量,以及心房、肾、胰腺、脾、脑组织中ANF含量。动物随机分为3组:对照组、心得安组和异搏定组。结果血浆ANF件别为26.89±2.95,20.80±6.77(P<0.01),13.76±4.69(P<0.01)ng/ml,实验组均显著降低,血浆AVP对照组为13.65±0.92,心得安组为2364±15.29(P<0.01)显著升高,异搏定组为12.58±1.85(P<0.05)pg/ml显著降低。实验组脑干ANF明显降低;左右心房、脑半球ANF明显升高。提示:SHR血浆及所测组织中均有ANF或ANF样免疫活性物质存在,且在降压过程中,ANF合成与释放均有明显改变并与AVP相互制约共同发挥调节作用。     

阿托伐他汀对自发性高血压大鼠血压、循环和心肌血管紧张素Ⅱ水平的影响

目的：观察阿托伐他汀对自发性高血压大鼠（SHR）血压、循环和心肌血管紧张素Ⅱ(Ang Ⅱ)水平的影响。 方法: 24只SHR随机分为4组（每组6只）：SHR对照组、阿托伐他汀50 mg组、阿托伐他汀10 mg组和缬沙坦组, 6只WKY大鼠作为正常血压对照组（WKY组）。给药前和给药后每两周测量大鼠尾动脉收缩压（SBP）。测定血清脂质及血浆和心肌血管紧张素Ⅱ（AngⅡ）水平。 结果: SHR各组SBP于给药前无显著差异（P>0.05），但均显著高于WKY组（P<0.01）；给药后第4、6周,阿托伐他汀50 mg组SBP明显低于SHR对照组（P<0.01）,10 mg组则不明显；缬沙坦组自给药后第2周，SBP进行性下降（P<0.01）。SHR对照组与WKY组血脂各项指标无显著差异（P>0.05）；阿托伐他汀50 mg组TC、TG及LDL-C水平明显低于SHR对照组（P<0.05，P<0.01），10mg组仅LDL-C水平明显下低于SHR对照组（P<0.05）。SHR对照组血浆AngⅡ浓度无明显差异，但心肌AngⅡ浓度明显高于WKY组（P<0.05）；给药6周后，阿托伐他汀各剂量组和缬沙坦组血浆AngⅡ浓度显著高于SHR对照组（均P<0.01），而心肌AngⅡ浓度在阿托伐他汀50 mg组和缬沙坦组明显低于SHR对照组（P<0.05）。 结论: 阿托伐他汀能降低SHR的血压，机制可能与降低心肌AngⅡ浓度含量有关。     

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。     

血栓素A_2和前列腺环素与自发性高血压大鼠高血压发展的关系

本文观察了SHR和WKY及不同年龄SHR动脉血浆中TXA_2和PGI_2的稳定代谢产物TXB_2和6-Keto-PGF_(1α)的浓度及其比值变化。结果表明,SHR血浆中的TXB_2浓度显著高于WKY,对照组与实验组相比(207.1±59.8比1217.9±298.5P8/ml,P<0.001),而血浆中6-Keto-PGF_(1α)浓度,除高年龄组SHR外,其他各组均无明显改变;SHR各组血浆中6-Keto/TXB_2比值均显著低于WKY组,不同年龄组SHR血浆中TXB_2浓度相比,高年龄组明显高于低年龄组(2184.5±273.1比1290.6±284.4pg/ml,P<0.001),高年龄组血浆中6-Keto-PGF_(1α)浓度虽有升高,但6-Keto/TXB_2比值仍明显低于对照组(0.21±0.12比1.48±0.78,P<0.001)。这些变化可能与SHR高血压的持续发展有关。     

Losartan抗高血压左室肥厚的细胞学机制研究

目的:探讨细胞增殖与细胞凋亡在高血压左室肥厚中的作用及血管紧张素Ⅱ1型受体(AT₁受体)拮抗剂在体干预对其影响。方法:选用成年12及24周龄SHR和WKY大鼠,干预组SHR自12周龄起每日胃管灌饲losartan(15mg·kg^-1·d^-1)至24周龄止。称重法测量左室肥厚指数,免疫组化法检测PCNA的蛋白表达,TUNEL法原位检测细胞凋亡,半定量RT－PCR法检测fas mRNA表达。结果:SHR左室肥厚指数、心肌细胞凋亡率显著多于同龄WKY(P＜0.01),心肌成纤维细胞凋亡率显著低于同龄WKY(P＜0.05)。12周龄SHR心肌细胞PCNA阳性率显著高于同龄WKY(P＜0.05),心肌成纤维细胞阳性率在两组间无显著差异。24周龄WKY和干预组SHR无PCNA阳性细胞检出,24周龄SHR偶见阳性心肌细胞。干预组左室肥厚指数、心肌细胞凋亡率显著低于同龄SHR组,成纤维细胞凋亡率显著高于同龄SHR组。各组大鼠心肌组织中fasmRNA表达量与细胞凋亡率呈正相关(r=0.52,P＜0.05)。结论:成年SHR左室肥厚的细胞学变化表现为心肌细胞的增殖/凋亡的失衡,以及心肌成纤维细胞凋亡的减少。losartan抗成年SHR左室肥厚的机制可能与改变这种异常的细胞群体变化及调节fas基因的表达有关。     

原发性高血压大鼠血浆外泌体水平及其与微循环变化的相关性研究

目的:研究13周龄原发性高血压大鼠(SHR)外周血外泌体数量和大小分布与微循环功能的相关性。方法:市购13周龄雄性SHR(实验组)和相同周龄的WKY大鼠(对照组)各7只。采用多功能激光多普勒血流探测仪(LDF)检测两组大鼠耳廓、趾及脑皮质血流量、血细胞聚集度和血流速度,采用血流成像技术(LDPI)观察脑皮质血流分布。取外周血,提取血浆外泌体,采用透射电镜观察外泌体形态,以Apogee流式细胞术检测总外泌体水平和直径100nm的外泌体水平,分析实验组大鼠外泌体水平与其微循环指标的相关性。结果:LDF结果显示,实验组大鼠脑皮质血流量和血流速度均显著高于对照组(P0.05或P0.01),而实验组大鼠趾血流量和血流速度明显低于对照组(P0.05),两组大鼠的耳廓血流量、血流速度及耳廓、趾和脑皮质的血细胞聚集度差异均无统计学意义(P0.05);LDPI结果显示,实验组大鼠脑皮质血流灌注量显著高于对照组(P0.01)。体外实验显示,实验大鼠血浆外泌体大小分布不均,但以直径100nm者居多;实验组总外泌体水平和直径100nm外泌体水平均明显高于对照组(P0.05)。相关性分析显示,实验组大鼠血浆总外泌体和直径100nm外泌体水平与脑皮质血流量呈显著正相关(P0.01)。结论:脑微循环功能改变与血浆总外泌体含量,尤其直径100nm的外泌体水平显著相关,提示外泌体水平的升高可能预警原发性高血压发生和发展过程中的微循环变化,或可作为高血压早期的监测标记物。     

L-苯丙氨酸对自发性高血压大鼠血液NO、ET和SOD水平的影响

目的： 探讨苯丙氨酸对自发性高血压大鼠(SHR)血浆NO、ET和SOD水平的影响。方法: 以11只4周龄雄性SHR 为实验对象,分为苯丙氨酸饲喂组（n=6）及对照组（n=5）;另以相同周龄的WKY大鼠（n=6）作为正常对照组。至实验大鼠30和42周龄时，检测血浆NO、ET和SOD的水平。结果: SHR血浆NO水平明显高于WKY (P<0.01)，血浆ET水平明显低于WKY (P<0.01)；苯丙氨酸治疗后抑制SHR血压的上升，血浆SOD及ET水平明显上升(P<0.01)；血浆NO水平明显下降(P<0.01)。结论: 苯丙氨酸可调节氧自由基的清除和改善内皮细胞的内分泌功能，这可能是苯丙氨酸新的降低血压的机制。     

高血压病伴房颤患者血浆内皮素与心钠素含量测定的意义

应用放免法测定６４例原发性高血压病Ⅱ期患者血清内皮素与心钠素含量,并以３４名健康者作对照。高血压病患者血清ＥＴ与ＡＮＰ均高于正常对照。高血压病伴房颤患者血清ＡＮＰ虽然比不伴房颤患者高,但无统计学意义;而前者血清ＥＴ则明显高于后者,即高血压病伴房颤患者ＥＴ水平高。     

Atrial natriuratic peptide and experimental vasorenal hypertension in rats

Vasorenal hypertension in rats resulted in increase of arterial pressure, the plasma concentration of creatinine and potassium. By EM immunocytochemistry we have demonstrated that atrial natriuretic peptide (ANP) was kept in the granules of secretory cardiomyocytes of the right atrium. It has shown that cardiomyocytes released ANP by means of diffusion. The increased secretion of atrial natriuretic peptide has been detected in blood. However the physiological effects this peptide probably was impaired due to the reducing of the density of natriuretic peptide receptors.     

Pathophysiologic role of natriuretic peptides

To evaluate the pathophysiologic role of atrial natriuretic peptide (ANP) in hypertension, hemodynamic effects of human ANP and antiserum against rat ANP were investigated in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Intravenous administration of human ANP caused greater hypotension associated with a decrease of cardiac output in SHR than in WKY, which suggests that SHR have enhanced responsiveness to exogenous ANP. The antiserum increased blood pressure and cardiac output, with the latter being significantly greater in SHR than in WKY. These results suggest that endogenous ANP counteract, in part, the maintenance of hypertension. In addition, hemodynamic and renal excretory effects of brain natriuretic peptide (BNP), a novel natriuretic peptide identified from porcine, were studied in SHR and WKY. BNP caused marked natriuresis and hypotension in a dose-dependent fashion, as observed with ANP. Not only ANP but also BNP may have a role in the regulation of blood pressure and water-electrolyte balance.     

Development of immunoreactive atrial natriuretic peptide in fetal hearts of spontaneously hypertensive and Wistar-Kyoto rats

Summary The development of immunoreactive atrial natriuretic peptide (ANP) was studied in fetal hearts of spontaneously hypertensive (SHR) and compared to normotensive Wistar-Kyoto (WKY) rats. While SHR fetal hearts were noticeably less developed than those of WKY at 10 and 11 days gestation, both strains showed ANP immunoreactive cells in some but not all primitive heart tubes. At 12 days additional ANP immunoreactive cells appeared in formative trabeculae of the ventricle and atrium. ANP cells were also observed in the myogenic layer of the truncus and bulbus arteriosus and their derivatives from 11 through 16 days, but not at 18 days. In both strains, there were more ANP cells in the left ventricle than in right beginning at day 13. There were no obvious strain differences in the developmental pattern and timing of ANP producing cells. However, on the day of birth, staining was reduced in hearts from some WKY newborn pups compared with hearts from SHR newborns and ventricular staining was reduced in both strains when compared to fetal hearts. These observations indicate that ANP is one of the earliest peptide hormones produced and that the predisposition to genetic hypertension does not appear to influence the development of ANP.     

高血压患者离体胃动脉平滑肌细胞内心钠素和内皮素的测定

采用正常血压者（ＮＴ）和高血压患者（ＥＨ）的离体动脉血管，并分离，培养动脉平滑肌细胞（ＡＳＭＣ），观察了ＡＳＭＣ合成和分泌心钠素（ＡＮＰ）内皮素（ＥＴ）的情况，探讨它们之间的相互关系及在高血压发病中的作用，结果发现：体外培养和ＡＳＭＣ能够合成和分泌ＡＮＰ，ＥＴ。ＥＭ组ＡＳＭＣ及培养液中的ＡＮＰ和ＥＴ含量显著高于ＮＴ组（Ｐ〈０．０１），ＥＴ与ＡＮＰ呈显著正相关（ｒ＝０．９２，Ｐ〈０．０１）ＥＴ与收缩     

Differences between natriuretic peptide receptors in the olfactory bulb and hypothalamus from spontaneously hypertensive and normotensive rat brain

Natriuretic peptide receptor-A (NPR-A) functional characteristics in the hypothalamus and olfactory bulb (OB) have been investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Autoradiographic studies demonstrate a decreased number of atrial natriuretic peptide (ANP) binding sites in the olfactory bulb and hypothalamus in SHR compared to WKY rats. We found that NPR-A showed a lower maximal binding capacity (B(max)) and higher affinity in SHR than in WKY rats both in the olfactory bulb and hypothalamus. However, despite the lower B(max) in SHR, both ANP(1-28) and ANP(5-25) stimulated similar or greater cGMP production than in WKY rats. These differences were found even before the development of hypertension. NPR-A in the olfactory bulb and hypothalamus from 3-week-old SHR showed a lower B(max) and K(d) and a higher cGMP production rate than in WKY rats, suggesting that these characteristics are intrinsic of NPR-A in SHR, instead of being a result of hypertension itself. The present study provides evidences for altered NPR-A receptor properties and function in the olfactory bulb and hypothalamus from SHR, which might be involved in the pathogenesis of hypertension.     

EH患者血清利钠多肽及血栓素B_2水平的分析

目的：探讨原发性高血压（EH）患者血清ANP、BNP、CNP及TXB2水平的变化及其临床意义。方法：30例EH患者和正常人对照组分为2组;不同EH分期Ⅰ、Ⅱ、Ⅲ期分为3组,将测定结果进行统计分析。四项血清标志物均采用放射免疫分析。结果：EH患者组ANP、BNP、CNP及TXB2四项血清指标水平均较对照组升高非常显著（P均〈0.01）。Ⅰ期组EH患者血清ANP、CNP及TXB2三项血清标志物与对照组比较差异均无显著性（P均〉0.05）,而血清BNP则显著高于对照组（P〈0.05）;Ⅱ期组患者ANP水平显著高于Ⅰ期组和对照组（P〈0.05）,而BNP、CNP和TXB2三项血清标志物则非常显著高于Ⅰ期组和对照组（P均〈0.01）。Ⅲ期组结果显示,ANP、BNP、CNP和TXB2四项血清标志物均非常显著地高于Ⅱ期组、Ⅰ期组及对照组（P均〈0.01）,相关分析结果显示,患者ANP、BNP和CNP三项指标与自身的平均动脉压呈显著正相关（r=0.298,P〈0.01;r=0.409,P〈0.01;r=0.412,P〈0.01）。结论：本文四项血清指标水平显著升高,测定数据的变化与EH的发病及病情进展有关。     

Effects of chronic salt loading on plasma atrial natriuretic peptide (ANP) in the spontaneously hypertensive rat

Plasma concentrations of immunoreactive atrial natriuretic peptide (ANP) was measured in spontaneously hypertensive rats (SHR) during chronic salt loading (1.5% NaCl in drinking water). During the 3-week experimental period mean arterial blood pressure, heart rate, urinary sodium excretion and body weight was assessed in salt-loaded as well as in control rats. The sodium excretion was more than 10-fold increased in the rats on the high salt diet. The plasma ANP concentration was significantly increased only 24 h after the start of the high salt intake. Thereafter plasma ANP concentrations were not significantly different from values obtained in control rats. The blood pressure was significantly increased after 3 weeks on the high salt diet. At the end of the 3-week experimental period the rats were subjected to a 10 and 20% acute volume expansion with homologous whole blood. During this intervention the increase in plasma ANP concentrations was blunted in the high salt rats compared to the control group. It is concluded that during chronic salt loading in SHR there is an initial rise in plasma ANP levels and that other hormonal and neuronal systems are more important in the long term maintenance of fluid and electrolyte balance.     

Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats

Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) both have diuretic, natriuretic, and hypotensive effects, and both are involved in cardiovascular homeostasis as cardiac hormones. To study the effects of HHE on the natriuretic peptide synthesis system, 170 male Wistar rats were housed in a chamber at the equivalent of the 5500-m altitude level for 1-12 weeks. After 1 week of HHE, pulmonary arterial pressure was significantly raised, and the ratio of left ventricle plus septum over right ventricle of the heart showed a significant decrease (compared with those of ground-level control rats). In both ventricular tissues, the expression of ANP messenger (m)RNA and BNP mRNA increased after exposure to HHE. The amounts of ANP and BNP had decreased significantly in right atrial tissue at 12 weeks of HHE (compared with those of the controls), whereas in ventricular tissues at the same time point, both levels had increased significantly. In in situ hybridization and immunohistochemical studies, the staining of the mRNAs for ANP and BNP and of ANP and BNP themselves was more intense in both ventricular tissues after exposure to HHE than before (i.e., in the controls). The results suggest that, in response to HHE, the changes in ventricular synthesis are similar for ANP and BNP. These changes may play a role in modulating pulmonary hypertension in HHE. However, under our conditions, pulmonary hypertension increased progressively throughout the HHE period.