Nitric Oxide in Hypertension and Renal Diseases

Nitric oxide (NO) is intimately involved in the regulation of vascular tone, renal haemodynamics and sodium balance. The physiological actions of NO suggest important vascular and renal protective roles for NO. When produced in large amounts, however, NO may also mediate cytotoxic effects. Increasing evidence suggests that endothelial function, notably the NO pathway, may be compromised in hypertension. It is not known, however, whether changes in endothelial function are primary or secondary to the development of hypertension. In renal diseases evidence for both excessive and deficient activity of NO pathway has been found. Increased glomerular production of NO via inducible NO synthase (NOS) with potential cytotoxic consequences has been demonstrated in experimental acute glomerulonephritis. On the other hand, indirect evidence obtained by means of NOS inhibitors point out to an important renoprotective role for NO in renal diseases. NO may counteract disease progression in renal diseases by preventing glomerular microthrombi, maintaining renal perfusion and medullary oxygenation, and via its anti-inflammatory/antiproliferative effects. However, these beneficial effects of NO may be compromised (endothelial and/or tubular dysfunction) in chronic nephropathies resulting in an accelerated course of renal disease. In future, more specific inhibitors and activators of different NOS isoforms are needed to elucidate the role of NO in various renal diseases in detail, and for treatment strategies aimed at modifying the NO pathway.     

高血压患者冠状动脉血流储备下降对左室舒张功能减退的影响

目的 探讨血压控制达标的高血压患者冠状动脉血流储备（Coronary flow reserve, CFR）对左室舒张功能的影响。 方法 86例血压控制达标且经冠脉造影或冠脉CT检查证实冠脉狭窄<50%的高血压患者,行经胸多普勒超声心动图ATP负荷试验检测冠状动脉左前降支的CFR;测定ATP负荷前后左室舒张功能参数,包括舒张早期、舒张晚期二尖瓣血流速度（E、A）和左心室侧壁及间隔二尖瓣环舒张早期、舒张晚期运动速度（Em、Am）,分析CFR与左室舒张功能参数的关系。 结果 入组患者总体CFR为2.85±0.67,其中CFR<3者47人（54.65%）,CFR为2.35±0.40,CFR≥3者39人（45.35%）,CFR为3.45±0.36;CFR<3的患者CFR与ATP负荷后侧壁Em呈正相关（r=0.42,P=0.003）,多元线性回归分析显示CFR为ATP负荷后侧壁Em的独立影响因素（P=0.015）。 结论 血压控制达标且排除冠心病的高血压患者约50%存在冠脉微循环障碍;有微循环障碍的高血压患者CFR下降是左室舒张功能减退的独立影响因素。     

高血压患者冠状动脉血流储备下降对左心室舒张功能减退的影响

目的 探讨血压控制达标的高血压患者冠状动脉血流储备（CFR）对左心室舒张功能的影响。方法 对86例血压控制达标、且经CAG或冠状动脉CTA证实冠状动脉狭窄<50%的高血压患者行经胸多普勒超声心动图ATP负荷试验,检测冠状动脉左前降支的CFR;测定ATP负荷前后左心室舒张功能参数,包括舒张早期、舒张晚期二尖瓣血流速度（E、A）和左心室侧壁及间隔二尖瓣环舒张早期、舒张晚期运动速度（Em、Am）,分析CFR与左心室舒张功能参数的关系。结果 入组患者总体CFR为2.85±0.67,其中47例CFR<3（2.35±0.40）,39例CFR≥3（3.45±0.36）。CFR<3时,CFR与ATP负荷后侧壁Em呈正相关（r=0.42,P=0.003）,且为ATP负荷后侧壁Em的独立影响因素（P=0.015）。结论 血压控制达标且排除冠心病的高血压患者中,约50%存在冠状动脉微循环障碍;有微循环障碍的高血压患者CFR下降是左心室舒张功能减退的独立影响因素。     

Renal functional reserve in kidney donors

The glomerular filtration rates of 28 subjects, who had undergone donor nephrectomy up to 22 years previously, were measured before and after ingestion of an 80 g protein meal. A renal functional reserve was demonstrated in all cases. There was no evidence of loss of this reserve with time after nephrectomy. This study supports the view that long-term compensatory hyperfiltration of the remaining kidney after donor nephrectomy is not damaging, at least over this time scale.     

肥胖对老年高血压左室肥厚和左心功能的影响

目的：探讨肥胖对老年高血压左室肥厚和左心功能的影响。方法：应用超声心动图检测50例老年高血压伴肥胖者左室重量、左室重量指数和左心功能，并取53例老年高血压非肥胖者作为对照。结果：肥胖组左室重量和左室重量指数均明显高于非肥胖组（P〈0．01）；肥胖组左室肥厚检出率也较非肥胖组明显增高（P〈0．01），前者发生左室肥厚的相对危险度是后者的2．12倍。肥胖组峰值速度E／峰值速度A比值均明显下降（P〈0．01），而峰值速度A和左室射血分数变化不明显（P〉0．05）。结论：肥胖对老年高血压左室肥厚有促进作用，可引起舒张功能障碍。     

腹型肥胖对高血压患者血压变异性的影响

目的评估腹型肥胖对原发性高血压患者血压变异性的影响。方法选择2014年1月至2014年4月核工业416医院收治的单纯性高血压患者159例,根据患者腹围分组,腹围正常者(男性90 cm,女性85 cm)72例为对照组,其中男38例,女34例;合并腹围增高者(男性≥90 cm,女性≥85 cm)87例为观察组,其中男45例,女42例。所有患者行24 h动态血压监测(ABPM),观察患者血压变异性(BPV)的特点。结果观察组24 h收缩压变异系数、日间平均收缩压变异系数均高于对照组,差异有统计学意义(P0.05);两组男性患者夜间平均舒张压变异系数均高于女性患者,差异有统计学意义(P0.05);且观察组男性患者24 h收缩压变异系数高于女性患者,差异有统计学意义(P0.05)。结论腹型肥胖时,高血压患者BPV增高,且男性患者较女性患者明显。     

吲哚氰绿试验联合血栓弹力图补充Child-Pugh分级在评估门脉高压手术患者肝储备功能中的应用

目的:探讨以吲哚氰绿试验(ICG measurement)和血栓弹力图(TEG)补充Child-Pugh分级所形成的新的肝储备评分系统(Ditan 分级)在评估肝硬化门静脉高压症患者肝储备功能中的可行性.方法:对2006年10月至2009年10月间91例肝硬化门静脉高压症接受联合断流术病例,分别于术前和术后以Child-Pugh与Ditan评分系统评估肝储备功能,了解两种方法预测术后肝功能代偿情况的准确率.结果:Child-Pugh分级法和Ditan分级法预测术后肝功能代偿良好准确率分别为57.89%和89.29%(P<0.05);Child-Pugh分级法和Ditan分级法预测术后肝功能代偿轻度不良准确率分别为68.66%和86.21%(P<0.05).结论:Ditan分级系统较Child-Pugh评分能够更全面评价肝硬化门静脉高压症患者围手术期肝储备功能.     

超声新技术在评价肝储备功能方面的应用

肝脏储备功能反映的是肝脏潜在的能力,特别体现在对手术的耐受程度及肝损伤后的恢复能力上,有较强的预测性。本文对超声新技术在评价肝储备功能方面的应用作一综述,为手术的实施和方法及判断预后提供依据。     

Renal functional reserve in patients with essential hypertension: effect of inhibition of the renin--angiotensin system

1. Urinary albumin excretion and the effect of an acute oral protein load (a meat meal) on glomerular filtration rate ('renal functional reserve') were evaluated in 15 essential hypertensive patients with preserved renal function and compared with 12 normal subjects. 2. Seven patients had microalbuminuria (greater than 30 mg/day) that was not correlated with blood pressure values. 3. After an oral protein load, an average increase of 20% in glomerular filtration rate (from 91 +/- 19 to 110 +/- 27 ml min-1 1.73 m-2 was found in the hypertensive patients. This change was not statistically different from that observed in normal controls (from 102 +/- 7 to 124 +/- 9 ml min-1 1.73 m-2). The glomerular response in hypertensive patients was independent of age, duration of hypertension, blood pressure, plasma renin activity, urinary albumin excretion and retinal vascular alterations. 4. All patients were re-evaluated after 6 weeks treatment with a new orally active angiotensin-converting enzyme inhibitor, benazepril. Systolic, diastolic and mean blood pressures were lowered in all the patients, but the drug did not affect the glomerular response to acute protein ingestion or the magnitude of urinary albumin excretion. 5. The findings of a normal 'renal functional reserve' and a lack of change in both urinary albumin excretion and the glomerular response after angiotensin-converting enzyme inhibition cast doubt on the existence of increased intraglomerular pressure in hypertensive patients.     

Renal reserve filtration capacity in growth hormone deficient subjects

Abstract. In normal subjects, the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) acutely increase in response to infusion of amino acids and to low doses of dopamine. It is uncertain whether circulatory growth hormone (GH) is a permissive factor for these stimulatory effects. GFR and ERPF (constant infusion technique using ¹²⁵I-iothalamate and ¹³¹I-hippuran, respectively) were measured before and during the infusion of dopamine and amino acids in 8 GH deficient subjects. The clearance study was repeated during concomitant administration of octreotide to investigate whether this somatostatin analogue would modify the amino acid and dopamine-induced renal haemodynamic changes. Dopamine increased baseline GFR from 89± 3 (mean±SEM, n= 8) to 102 ± 4 ml min^-1 1.73 m^-2 and ERPF from 352± 19 to 476± 26 ml min^-1 1.73 m^-2, P<0.001 for both. During amino acid infusion GFR and ERPF increased to 108±3 and 415±23 ml min^-1 1.73 m^-2, respectively, P< 0.001 for both. Octreotide did not significantly decrease baseline and dopamine-stimu-lated renal haemodynamics but lowered the amino acid-stimulated GFR (98±4 ml min^-1 1.73 m^-2, P<0.05) and ERPF (381± 18 ml min^-1 1.73 m^-2, P<0.05). Basal plasma glucagon concentrations were not suppressed by octreotide, whereas the amino acid-induced increments in plasma glucagon were partially inhibited. It is concluded that GH is not a necessary factor for the stimulatory effects of amino acids and dopamine on renal haemodynamics. The renal reserve filtration capacity in GH deficiency was at least as large as previously documented in normal subjects. It is likely that there is a functional antagonism between the effects of amino acids and octreotide on renal haemodynamics in GH deficiency.     

功能影像学评估肝脏储备功能研究进展

评估肝脏储备功能具有重要的临床意义,可确定肝切除的安全范围,早期识别潜在的肝损伤,评价中晚期肝病的治疗效果并判断预后等。评估肝脏储备功能的方法多样,吲哚菁绿（ICG）清除试验是目前临床较常用的方法,其应用价值已得到广泛认可。随着功能影像学的发展,无创或微创,更便捷、准确、全面地评估肝脏储备功能成为可能。本文对影像学评估肝脏储备功能的研究进展及其与ICG清除试验的关系进行综述。     

血压变化对心肌超声造影评定冠状动脉储备的影响

目的　探讨高血压对心肌超声造影评定冠状动脉 (冠脉 )储备的影响。方法　对 9只非开胸猪进行心肌超声造影。取乳头肌水平短轴观 ,以 0 .5ml/min的速度连续滴注造影剂BR1。每 15个心动周期进行 1次破泡。破泡后的再充盈时间 -强度关系可用公式y =A(1-e-bt) +c表示 ,依此可得到信号增加率b。以静息时的b参数除滴注腺苷后的b参数所得到的商为冠脉储备 ,并与荧光微球技术测得的心肌血流及冠脉储备进行对照。结果　苯肾上腺素使血压从 12 9/ 10 0mmHg(1mmHg =0 .13 3kPa)增加到 196/153mmHg(P <0 .0 0 1) ,心率由 114次 /min增加到 12 4次 /min(P>0 .0 5)。滴注苯肾上腺素前用两种方法测得的冠脉储备值类似 ,分别为 2 .5和 3 .1。苯肾上腺素导致的血压增高增加静息时的b值 ,降低腺苷扩血管后的b值 ,使冠脉储备明显降低 ,为 1.5(P <0 .0 5) ;用荧光微球技术测量所得的冠脉储备也明显降低 ,为 1.8。结论　苯肾上腺素导致的高血压可降低心肌超声造影所评定的冠脉储备值     

Renal functional reserve in patients with Type 1 diabetes mellitus

AIM: Decreased renal functional reserve might precede incipient diabetic nephropathy in patients with Type 1 diabetes. The aim of this study was to assess the relationship between renal functional reserve and easily assessable estimates of systemic endothelial dysfunction in normoalbuminuric patients with Type 1 diabetes and diabetic retinopathy. METHODS: Renal functional reserve was calculated as the relative change in glomerular filtration rate after protein ingestion. Glomerular filtration rate was measured using pharmacokinetic compartmental analysis of single-shot plasma sinistrin clearance. We measured the activity of von Willebrand factor and concentrations of C-reactive protein and apolipoprotein B, as easily assessable estimates of systemic endothelial dysfunction. RESULTS: Twenty-two patients were studied. Renal functional reserve was inversely associated with activity of von Willebrand factor (R=-0.431, p=0.045) and, in a multivariate model, with concentration of C-reactive protein (R=0.652, p=0.031). CONCLUSION: Renal functional reserve is inversely associated with concentration of C-reactive protein in normoalbuminuric patients with Type 1 diabetes and diabetic retinopathy. This finding provides evidence that decreased renal functional reserve might reflect endothelial dysfunction. We speculate that decreased renal functional reserve might possibly show as an early marker of diabetic nephropathy.     

Impaired synthesis and action of antiaggregating cyclic nucleotides in platelets from obese subjects: possible role in platelet hyperactivation in obesity

BACKGROUND: Subjects with central obesity exhibit platelet hyperactivity, which is involved in the atherosclerotic process and therefore can account for the increased risk of cardiovascular morbidity and mortality. The aim of the study was to evaluate whether alterations of platelet function in obesity involve synthesis and/or action of the two antiaggregating cyclic nucleotides adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP). MATERIALS AND METHODS: In platelets from 16 obese and 15 control subjects we investigated the influence on platelet responses to the Adenosine-5-diphosphate sodium salt (ADP) exerted by (i) prostacyclin analogue Iloprost (0.31-5 nmol L(-1)) and the cAMP analogue 8-bromo-cAMP (10-500 micro mol L(-1)); and by (ii) nitric oxide (NO) donor sodium nitroprusside (SNP) (5-100 micro mol L(-1)) and the cGMP analogue 8-bromo-cGMP (10-500 micro mol L(-1)). IC(50) (minimal concentration of each inhibitor necessary to reduce platelet response to ADP by half) was determined. Iloprost and SNP ability to increase cyclic nucleotides was also measured. RESULTS: Significantly greater IC(50) were observed in obese subjects than in healthy controls (1.59 +/- 0.16 vs. 0.80 +/- 0.08 nmol L(-1), P = 0.0001 for Iloprost, and 27.6 +/- 6.5 vs. 7.0 +/- 1.7 micro mol L(-1), P = 0.006, for SNP); when data from control and obese subjects were pooled together, IC(50) of Iloprost and SNP correlated with the homeostasis model assessment (HOMA IR), which is a parameter used to measure the insulin resistance (r = 0.588, P = 0.029 and r = 0.640, P = 0.006, respectively). Also the antiaggregating effect of 8-Br-cAMP and 8-Br-cGMP was smaller in the obese subjects. Finally, the ability of Iloprost to increase platelet cAMP and the ability of SNP to increase both cGMP and cAMP were reduced in obese subjects. CONCLUSIONS: Platelet resistance to the antiaggregating effects of prostacyclin and NO in obesity is attributable to impairment of cyclic nucleotide synthesis and action. As cyclic nucleotides are the main effectors of platelet antiaggregation, the resistance to them can account for platelet hyperactivity in obesity.     

冠脉血流显像技术无创性评价轻度高血压患者冠脉血流储备

目的　了解轻度高血压是否存在冠脉循环的功能性损害。方法　应用经胸超声心动图冠脉血流显像技术测量 2 3例无症状轻度高血压患者在静脉输注潘生丁溶液结合等长握力负荷状态下前降支冠脉血流的速度变化 ,并与 2 1例正常健康者对照。结果　轻度高血压组最大冠脉血流与基础冠脉血流速度比值较对照组降低 (峰值速度比为 3 .0 2± 0 .64vs 3 .77± 0 .5 8,P <0 .0 5 ) ,最小冠脉血管阻力指数较对照组增大 ( 0 .3 4± 0 .0 6vs 0 .2 6± 0 .0 8,P <0 .0 5 ) ,舒张功能出现轻度异常。两组左室腔径、左室重量和左室收缩功能无明显改变。结论　无症状的轻度高血压患者可出现冠脉储备降低和舒张功能异常。冠脉血流显像技术为评估冠脉循环功能提供了无创、简便、实用的冠脉血流储备检测手段。     

肝储备功能定量评估的影像学研究进展

综述肝储备功能定量评估的影像学研究进展。准确评估肝脏储备功能,有利于降低肝脏部分切除术后并发症或肝移植术后移植物原发性无功能和早期移植物功能不良的发生率。     

益肾降压方对肾实质性高血压大鼠血浆内皮素和一氧化氮的影响

目的 :观察益肾降压方对肾实质性高血压 (RPH )大鼠血浆内皮素 (ET)和一氧化氮 (NO )的影响。方法 :采用肾大部切除法建立 RPH模型。随机分为实验组 (益肾降压方高剂量组、中剂量组、低剂量组 )、西药组(开博通 )、模型对照组 (生理盐水 )及正常动物对照组。每日灌胃 1次 ,连续 8周。第 8周后采血 ,测定血浆 ET和 NO的含量。结果 :RPH模型大鼠血浆 NO水平明显下降 (P<0 .0 5 ) ;中剂量的益肾降压方和西药开博通能明显升高 NO(与模型对照组相比 ,P均 <0 .0 5 ) ,而对 ET则无明显作用。结论 :益肾降压方可能通过影响 RPH大鼠 NO水平来实现其降压机制。     

高血压病各期肾动脉血流的双功彩色多普勒超声评价

本文检测了３０例正常人，９１例不同分期高血压病患者的肾动脉主干和段间动脉的血流频谱。结果：Ⅰ期组肾动脉主干和段间动脉血流频谱各项参数与正常对照组比较，均未见统计学差异（Ｐ＞０．０５）；肾血流量，血流速度和肾血管阻力均处于正常状态。Ⅱ期组肾动脉主干和段间动的ＲＩ明显高于Ｉ期组（Ｐ＜０．０１），Ｖｄｍｉｎ，Ｖｄｍａｘ／Ｖｓｍａｘ明显低于Ｉ期组（Ｐ＜０．０１），Ｑ，Ｖｓｍａ和Ｖｍｅａｎ在两组间异不明显（     

吲哚菁绿排泄试验与肝脏储备功能的相关性评价

目的探讨吲哚菁绿（ICG）排泄试验在肝脏储备功能评估中的临床价值。方法选取2012年1月至2014年5月吉林大学中日联谊医院接受吲哚菁绿排泄试验的肝脏疾病患者119例,分别测定ICG 15分钟滞留率（R15）、血浆清除率（K）、有效肝血流量（EHBF）,并采用Child-Pugh分级、MELD评分及t检验、线性回归分析,比较R15、K值与Child-Pugh分级、MELD评分的关系。结果随着Child-Pugh分级的递增,K值和EHBF下降,而R15升高。Child-Pugh A组R15（12.289±12.754）%,K值（0.172±0.069）/min;Child-Pugh B组R15（41.818±17.202）%,K值（0.063±0.026）/min;两组R15、K值比较存在统计学差异（P〈0.05）。将R15、K值与Child-Pugh分级、MELD评分进行相关性分析,均存在良好相关性,R15为正相关,K值为负相关。结论 R15、K值与Child-Pugh分级关系密切,R15相关性更加显著,提示R15是评估肝脏储备功能的准确、灵敏指标。     

Assessment of the left ventricular diastolic reserve in essential hypertension: the acute saline load test

OBJECTIVE: The aim of this study was to evaluate the significance of the development of a restrictive response to an acute saline load, defined as an increase in the ratio of peak early to peak late diastolic transmitral flow velocity (E/A ratio) associated with a decrease in the deceleration time, in patients with mild to moderate untreated hypertension. BACKGROUND: Recognised abnormal patterns of transmitral diastolic flow include, from 'best' to 'worst': prolonged relaxation, pseudonormalisation, and restrictive physiology. The common denominator of these transitions is the constellation of an increase in the E/A ratio associated with a decrease in deceleration time. PATIENTS AND METHODS: Sixteen normal control subjects (6 males, 10 females, age 51.6 +/- 6.9 years) and 24 patients with mild to moderate untreated hypertension (12 males, 12 females, age 46.8 +/- 7.5 years) underwent supine blood pressure measurement with sphygmomanometry, biochemical studies, and transthoracic M-mode, 2D, and Doppler echocardiography before and after an acute saline load (7 mL kg(-1), maximum 500 mL, NaCl 0.9% within 15 min IV). RESULTS: The baseline E/A ratio was lower (0.90 +/- 0.14 vs. 1.04 +/- 0.18; P < 0.01) and the deceleration time was longer (158.8 +/- 19.4 vs. 135 +/- 8.9 ms; P < 0.01) in patients with hypertension compared with normotensive controls. However, no patient with hypertension exhibited a transmitral flow velocity pattern compatible with typical prolonged relaxation. A restrictive response to the acute saline load was observed in 12 (50%) of the hypertensive and none of the control subjects. Hypertensive patients with a restrictive response to the acute saline load had a lower baseline E velocity (54.8 +/- 8.7 cm s(-1) vs. 66 +/- 6.4 cm s(-1); P = 0.003), a lower baseline E/A ratio (0.83 +/- 0.13 vs. 0.97 +/- 0.12; P = 0.015), and a longer deceleration time (167.5 +/- 15.4 ms vs. 150 +/- 19.5; P = 0.03) than hypertensive patients without such a response. CONCLUSION: A restrictive response to an acute saline load is indicative of a limited diastolic reserve in patients with mild to moderate untreated hypertension. Further studies are required in order to evaluate the significance of such a response with regards to risk stratification and efficacy of medical treatment in this patient population.