尿液水通道蛋白-2与低肾素型高血压关系的研究

目的探讨水通道蛋白-2（AQP2）与低肾素型高血压（LREH）发病机制的关系。方法选取LREH患者110例，分为1、2、3级高血压三个亚组，设置健康对照者40名，间接ELISA法检测尿液AQP2浓度，放射免疫法检测血浆血管加压素（AVP）浓度，监测平均动脉压（MAP），分析患者尿液AQP2浓度的变化及其与血浆AVP浓度、MAP之间的关系。结果LREH组不同血压级别三个亚组血浆AVP浓度、尿液AQP2浓度均高于健康对照组（t=2．99、t=3．01，P〈0．05），并随血压级别升高而升高（P均〈0．05）；尿液AQP2浓度与血浆AVP浓度、MAP之间均呈正相关（r=0．862、r=0．694、r=0．797，P〈0．05）。结论LREH患者肾脏集合管主细胞内AQP2穿梭、表达的增加，可能与LREH的水钠潴留机制密切相关     

低肾素型原发性高血压尿液水通道蛋白2水平的研究

该文探讨低肾素型原发性高血压(LRH)患者尿液水孔蛋白2(AQP-2)水平及其与血压之间的关系,并评价其对 LRH 的诊断价值。方法:根据血浆肾素活性将150例原发性高血压患者分为 LRH、正常肾素型和高肾素型3组,28例正常血压者作为对照组。采     

低肾素型原发性高血压尿液水通道蛋白2水平的研究

该文探讨低肾素型原发性高血压（LRH）患者尿液水孔蛋白2（AQP-2）水平及其与血压之间的关系，并评价其对LRH的诊断价值。方法：根据血浆肾素活性将150例原发性高血压患者分为LRH、正常肾素型和高肾素型3组，28例正常血压者作为对照组。采用酶联免疫吸附试验检测尿液AQP-2含量，用放射免疫分析法同步测定血浆血管加压素（AVP）水平。结果：LRH患者AQP-2、AVP水平均明显高于正常肾素型与高肾素型及对照组，分别为（77．6±12．4）VS（50．0±10．9）、（44．6±14．0）、（45．5±11．8）nmol／L，均P〈0．01；（5．39±1．55）VS（3．82±1．51）、     

水通道蛋白-4与缺血性脑水肿关系的研究进展

水通道蛋白(aquaporins,AQPs)是一组具有高度选择性的水通道特异蛋白家族,其中AQP4在脑内分布最多.AQP4是胶质细胞与细胞间液、脑脊液以及血管之间的水凋节和运输的重要结构基础,其主要功能是调节水平衡,并在脑水肿的形成、发展及转归过程中发挥重要作用.     

问接酶联免疫吸附法定量检测大鼠尿液水通道蛋白-2浓度

目的通过间接酶联免疫吸附测定（ELISA）法，检测正常大鼠不同水代谢状态下尿液水通道蛋白-2（AQP2）。方法收集大鼠正常，禁水24h以及水负荷状态（80ml／kg）下的尿液，用间接ELISA法检测尿液中AQP2。结果本方法批内差异系数6．5％，批间差异系数7％，灵敏度为112．5pmol／L；禁水24h后大鼠尿液AQP2／肌酐显著增加（P〈0．01），给予水负荷后尿液AQP2／肌酐显著降低（P〈0．01）；且尿渗量与尿液AQP2／肌酐呈正相关（r=0．952，P〈0．001）。结论间接ELISA法可以较好地检测大鼠尿液中AQP2。     

间接酶联免疫吸附法定量检测大鼠尿液水通道蛋白-2浓度

目的通过间接酶联免疫吸附测定(ELISA)法,检测正常大鼠不同水代谢状态下尿液水通道蛋白-2(AQP2)。方法收集大鼠正常,禁水24 h以及水负荷状态(80 ml/kg)下的尿液,用间接ELISA法检测尿液中AQP2。结果本方法批内差异系数6.5%,批间差异系数7%,灵敏度为112.5 pmol/L;禁水24 h后大鼠尿液AQP2/肌酐显著增加(P<0.01),给予水负荷后尿液AQP2/肌酐显著降低(P<0.01);且尿渗量与尿液AQP2/肌酐呈正相关(r=0.952,P<0.001)。结论间接ELISA法可以较好地检测大鼠尿液中AQP2。     

α-adducin基因型与低肾素型原发性高血压的关系

目的研究α-adducin基因Gly460Trp多态性与低肾素型原发性高血压的关系。方法聚合酶链反应(PCR)-聚丙烯酰胺凝胶电泳检测基因型,采用放射免疫分析法测定样本的血浆肾素活性(PRA)。结果α-adducin基因Gly460Trp突变没有损伤肾脏钠盐调控,不影响肾素水平,低肾素型原发性高血压与正常肾素型原发性高血压的基因型分布差异无统计学意义。结论α-adducin基因Gly460Trp多态性与低肾素型原发性高血压无相关性。     

低肾素型高血压研究进展

自 1 962年Conn首次发现并报道了原发性醛固酮增多症以来 ,将这一类以低血钾 ,低肾素为典型表现的高血压从“原发性高血压”中区别开来 ,称为低肾素型高血压 ,并在过去近 1 0年中揭示了其中几种单基因遗传形式 ,目前这一大类高血压病可分为原发性和继发性两个亚群。目前认为 ,低肾素型高血压约占高血压患者的30 %。随着上皮钠通道 (epithelialsodiumchannel,ENaC)亚单位的成功克隆 ,对低肾素型高血压的基础研究日渐深入。尤其是近十年来 ,已经从原先停留于疾病表象的认识发展到对疾病分子生物学基础的研究。现认为 ,低肾素型高血压的病理…     

脑钠素及水通道蛋白-2与原发性高血压关系的研究

目的探讨脑钠素（BNP）和水通道蛋白-2（AQP2）在原发性高血压发病机制中所起的作用。方法采用间接ELISA检测尿液AQP2浓度，用ELISA法检测血浆BNP浓度，并监测平均动脉压（MAP），分析各级高血压患者尿中AQP2浓度变化及其与血浆BNP浓度、MAP之间的关系。结果①左室肥厚组（LVH组）患者尿液AQP2浓度和血浆BNP浓度较健康对照组和无左室肥厚组（NLVH组）升高（P均〈0．01），且各亚组这两个指标随着血压的升高而增高，各亚组之间比较差异有统计学意义（P〈0．01）。②NLVH组尿液AQP2浓度和血浆BNP浓度高于对照组（P均〈0．05），但与血浆BNP浓度、血压水平无明显相关性（P〉0．05）。结论①BNP的检测有利于EH合并LVH早期诊断；②BNP有可能通过细胞信使分子之间的相互作用影响AQP2的表达。     

糖尿病大鼠肾脏髓质水通道蛋白2的表达和意义

目的 检测链脲佐菌素诱导的糖尿病（DM）大鼠。肾脏髓质集合管水通道蛋白2（AQP-2）的变化。方法 实验大鼠分为正常对照组（Con组）和糖尿病组（DM组）。在成模12周后，分别用光学显微镜、电子显微镜等方法观察。肾脏形态变化，用免疫组织化学、核酸原位杂交和逆转录PCR方法检测DM大鼠肾髓质集合管AQP-2的表达。结果 （1）实验初DM组与Con组之间血糖、体重差异无统计学意义（P〉0．05），但12周时DM组血糖明显升高（P〈0．01），尿量高于Con组（P〈0．01），体重明显低于Con组（P〈0．01），DM组相对。肾重高于Con组（P〈0．01），二组间血肌酐无明显变化（P〉0．05）。（2）DM组尿渗透压低于Con组（P〈0．05），血渗透压高于Con组（P〈0．05）。（3）DM组大鼠血浆加压素水平比Con组明显升高（P〈0．05）。（4）光镜下。肾脏结构未见明显改变，电镜下可见。肾脏髓质集合管亮细胞和暗细胞结构改变。（5）DM大鼠肾脏髓质集合管AQP-2mRNA及蛋白质的表达增加。结论 DM大鼠肾脏髓质AQP-2mRNA及蛋白质的表达增加，并伴有早期。肾脏病理改变。尿AQP-2有望作为糖尿病。肾病早期诊断指标。     

Neurogenic factors in low renin essential hypertension

The interrelationships between blood pressure, plasma catecholamines and plasma renin activity (PRA) were studied in 12 patients with low PRA, in 18 patients with essential hypertension and normal PRA and in 11 normal subjects, after being supine for 1 hour, standing 1 hour and after the oral administration of furosemide, 80 mg. Patients with low PRA were older and had higher (p < 0.05) mean blood pressure levels (113 ± 4.2 mg Hg) than patients with normal PRA (103 ± 1.9 mm Hg). Plasma norepinephrine levels were 145 ± 14 ng/liter in normal volunteer subjects, 202 ± 25 ng/liter in hypertensive subjects with normal PRA and 203 ± 26 ng/liter in hypertensive subjects with low PRA. The increase of plasma norepinephrine and epinephrine after standing 1 hour and after the administration of furosemide was similar in hypertensive subjects with low or normal PRA and in normal volunteer subjects. However, the increase in PRA after standing or after the administration of furosemide was significantly reduced in patients with low PRA. These data suggest that patients with low PRA have a normally responsive sympathetic nervous system and that the low PRA may be due to a defective renin response to the sympathetic nerve stimulation. Blood pressure was significantly correlated with plasma catecholamines in normal volunteer subjects (r = 0.71, p < 0.05) and in the hypertensive patients (r = 0.49, p < 0.05). An analysis of the regression lines for the two groups suggests that increased vascular reactivity to catecholamines may account for the increased blood pressure at each level of catecholamines in hypertensive subjects as compared to normal volunteer subjects. Basal plasma aldosterone levels were similar in patients with low and with normal PRA.Norepinephrine clearance was lower in hypertensive than in normotensive subjects.     

African Americans,hypertension and the renin angiotensin system

African Americans have exceptionally high rates of hypertension and hypertension related complications. It is commonly reported that the blood pressure lowering efficacy of renin angiotensin system(RAS) inhibitors is attenuated in African Americans due to a greater likelihood of having a low renin profile. Therefore these agents are often not recommended as initial therapy in African Americans with hypertension. However, the high prevalence of comorbid conditions, such as diabetes, cardiovascular and chronic kidney disease makes treatment with RAS inhibitors more compelling. Despite lower circulating renin levels and a less significant fall in blood pressure in response to RAS inhibitors in African Americans, numerous clinical trials support the efficacy of RAS inhibitors to improve clinical outcomes in this population, especially in those with hypertension and risk factors for cardiovascular and related diseases. Here, we discuss the rationale of RAS blockade as part of a comprehensive approach to attenuate the high rates of premature morbidity and mortality associated with hypertension among African Americans.     

Increased plasma vasopressin in low renin essential hypertension

Baseline plasma vasopressin concentrations were measured in 48 men (all 50 years old) with decreased plasma renin concentration and untreated, sustained essential hypertension and in 29 healthy normotensive men. Mean hypertensive plasma vasopressin concentration was more than twice as high as the corresponding normotensive level (15.7 +/- 2.2 [SE] vs 7.5 +/- 1.0 pg/ml; p less than 0.001). Plasma renin concentration in the hypertensive group was reduced compared with that in the normotensive group (0.28 +/- 0.04 vs 0.46 +/- 0.06 Goldblatt units X 10(-4)/ml). These differences appeared despite virtually identical serum osmolality, creatinine clearance, and urinary sodium excretion in the two groups. In the first 38 hypertensive subjects, arterial plasma epinephrine concentrations were significantly increased over those of the first 28 control subjects (99 +/- 12 vs 68 +/- 6 pg/ml; p less than 0.025). In contrast to those with low renin essential hypertension, 35 men with normal renin essential hypertension (all 40 years old) had normal plasma vasopressin levels that were not significantly different from those in a comparable normotensive control group (3.7 +/- 0.8 vs 3.5 +/- 0.4 pg/ml). Arterial epinephrine concentrations were not significantly different between normal renin subjects and the control group. After 6 weeks of treatment with the nonselective beta-adrenergic receptor blocker oxprenolol in 11 subjects with low renin hypertension, blood pressure was reduced and the plasma vasopressin concentration fell from 27.6 +/- 6.4 to 13.5 +/- 4.2 pg/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Potential pathophysiological role for the vitamin D deficiency in essential hypertension

Vitamin D deficiency has been indicated as a pandemicemerging public health problem. In addition to the well-known role on calcium-phosphorus homeostasis in thebone, vitamin D-mediated processes have been recentlyinvestigated on other diseases, such as infections, can-cer and cardiovascular diseases. Recently, both the dis-covery of paracrine actions of vitamin D(recognized aslocal vitamin D system) and the link of vitamin D with renin-angiotensin-aldosterone system and the fibroblast growth factor 23/klotho pathways highlighted its ac-tive cardiovascular activity. Focusing on hypertension, this review summarizes the more recent experimental evidence involving the vitamin D system and deficiency in the cardiovascular pathophysiology. In particular, we updated the vascular synthesis/catabolism of vitamin D and its complex interactions between the various endocrine networks involved in the regulation of blood pressure in humans. On the other hand, the conflicting results emerged from the comparison between obser-vational and interventional studies emphasize the frag-mentary nature of our knowledge in the field of vitamin D and hypertension, strongly suggesting the need of further researches in this field.     

Abnormal increase in urinary aquaporin-2 excretion in response to hypertonic saline in essential hypertension

Background

Secondary hyperparathyroidism (SHPT) is associated with mortality in patients with chronic kidney disease (CKD), but the economic consequences of SHPT have not been adequately studied in the European population. We assessed the relationship between SHPT parameters (intact parathyroid hormone [iPTH], calcium, and phosphate) and hospitalisations, medication use, and associated costs among CKD patients in Europe.

Methods

The analysis of this retrospective cohort study used records of randomly selected patients who underwent haemodialysis between January 1, 2005 and December 31, 2006 at participating European Fresenius Medical Care facilities in 10 countries. Patients had ?? 1 iPTH value recorded, and ?? 1 month of follow-up after a 3-month baseline period during which SHPT parameters were assessed. Time at risk was post-baseline until death, successful renal transplantation, loss to follow-up, or the end of follow-up. Outcomes included cost per patient-month, rates of hospitalisations (cardiovascular disease [CVD], fractures, and parathyroidectomy [PTX]), and use of SHPT-, diabetes-, and CVD-related medications. National costs were applied to hospitalisations and medication use. Generalised linear models compared costs across strata of iPTH, total calcium, and phosphate, adjusting for baseline covariates.

Results

There were 6369 patients included in the analysis. Mean ± SD person-time at risk was 13.1 ± 6.4 months. Patients with iPTH > 600 pg/mL had a higher hospitalisation rate than those with lower iPTH. Hospitalisation rates varied little across calcium and phosphate levels. SHPT-related medication use varied with iPTH, calcium, and phosphate. After adjusting for demographic and clinical variables, patients with baseline iPTH > 600 pg/mL had 41% (95% CI: 25%, 59%) higher monthly total healthcare costs compared with those with iPTH in the K/DOQI target range (150?C300 pg/mL). Patients with baseline phosphate and total calcium levels above target ranges (1.13?C1.78 mmol/L and 2.10?C2.37 mmol/L, respectively) had 38% (95% CI: 27%, 50%) and 8% (95% CI: 0%, 17%) higher adjusted monthly costs, respectively. Adjusted costs were 25% (95% CI: 18%, 32%) lower among patients with baseline phosphate levels below the target range. Results were consistent in sensitivity analyses.

Conclusions

These data suggest that elevated SHPT parameters increase the economic burden of CKD in Europe.