BACKGROUND & AIMS: How an increase in blood pressure, in and of itself, induces hypertensive nephrosclerosis is unclear. In an earlier study we found that leukocyte infiltration, proximal tubular cell proliferation, matrix deposition and interstitial fibrosis occur in the unclipped kidney of 2 K 1 C Goldblatt hypertensive rats. In this study we tested the hypothesis that the cell surface adhesion molecule ICAM-1 is expressed on the vascular endothelium and tubular epithelium of unclipped kidneys at 4 weeks. As a positive control, we examined the clipped kidney as well. We found that systolic blood pressure was significantly elevated in renovascular hypertensive rats compared to sham-operated controls after 4 weeks (198 +/- 5 mmHg vs 121 +/- 2 mmHg, P < 0.001). Furthermore, quantitative (densitometry) measurements showed that ICAM-1 expression on vascular endothelium and on tubular cells was significantly increased in unclipped kidneys compared to controls (P < 0.05). The same was true for monocyte and granulocyte infiltration (P < 0.05). These same variables were even more prominent in the clipped kidneys, compared to unclipped and control kidneys (P < 0.05). Our data show that ICAM-1 is expressed in unclipped kidneys exposed to hypertension as well as in clipped kidneys exposed to ischemia. We suggest that mechanical injury induced by increased blood pressure is responsible for an inflammatory adhesion molecule-mediated response and concomitant renal injury.

背景与目标： 血压升高本身如何引起高血压性肾硬化尚不清楚。在较早的研究中，我们发现2 K 1 C Goldblatt高血压大鼠的未切除肾脏中发生白细胞浸润，近端肾小管细胞增殖，基质沉积和间质纤维化。在这项研究中，我们测试了以下假设：第4周，细胞表面粘附分子ICAM-1在未切除的肾脏的血管内皮和肾小管上皮细胞中表达。作为阳性对照，我们还检查了修剪的肾脏。我们发现，与假手术对照组相比，肾虚血管高血压大鼠的收缩压在4周后显着升高（198 /-5 mmHg与121 /-2 mmHg，P <0.001）。此外，定量（密度测定）测量结果显示，与对照相比，未切除的肾脏在血管内皮和肾小管细胞上的ICAM-1表达显着增加（P <0.05）。单核细胞和粒细胞浸润也是如此（P <0.05）。与未修剪的和对照的肾脏相比，这些相同的变量在修剪的肾脏中甚至更为突出（P <0.05）。我们的数据表明，ICAM-1在暴露于高血压的未切除的肾脏以及暴露于缺血的切除的肾脏中表达。我们认为，血压升高引起的机械损伤是炎症粘附分子介导的反应和伴随的肾损伤的原因。

BACKGROUND & AIMS: :Surgically correctable forms of primary aldosteronism are generally held to be less common than forms requiring medical therapy. However, with the availability of improved diagnostic techniques and the adoption of a systematic and thorough diagnostic work-up they can be identified more commonly than expected. Adrenal vein sampling (AVS) for measurement of cortisol and aldosterone has emerged as the 'gold standard' diagnostic test for identifying unilateral causes of primary aldosteronism that are amenable to surgical cure. Adrenalectomy can provide long-term normalisation of blood pressure and correction of primary aldosteronism in about 55% of patients with an aldosterone-producing adenoma and can markedly ameliorate blood pressure control in the rest. This chapter summarises the diagnostic work-up suggested for identifying these forms and examines the other diseases mimicking mineralocorticoid excess that enter into the differential diagnosis of surgically curable primary aldosteronism.

背景与目标： ：通常认为可手术纠正的原发性醛固酮增多症形式不如需要药物治疗的形式普遍。但是，由于有了改进的诊断技术并采用了系统的，彻底的诊断方法，可以比预期的更为普遍地识别出它们。用于测定皮质醇和醛固酮的肾上腺静脉采样（AVS）已成为“金标准”诊断测试，用于识别可通过手术治愈的原发性醛固酮增多症的单方面原因。肾上腺切除术可在约55％的醛固酮生成腺瘤患者中提供长期的血压正常化和纠正原发性醛固酮增多症，并能显着改善其余患者的血压控制。本章总结了为鉴定这些形式而建议的诊断方法，并探讨了其他与模仿盐皮质激素过量有关的疾病，这些疾病已进入可手术治愈的原发性醛固酮增多症的鉴别诊断。

BACKGROUND & AIMS: :Persistent pulmonary hypertension of the newborn (PPHN) is a life‑threatening disease that is commonly observed in the neonatal intensive care unit. PPHN is pathologically characterized by pulmonary vascular remodeling and, in particular, pulmonary artery smooth muscle cell (PASMC) proliferation. Decreased expression levels of peroxisome proliferator‑activated receptor γ (PPAR‑γ), which is a member of the nuclear receptor hormone superfamily, in combination with elevated expressions of transient receptor potential cation channel, subfamily C, member 1 (TRPC1) and TRPC6 contributes to the PASMC proliferation and excessive pulmonary vascular remodeling in adult pulmonary hypertension (PH). Whether PPAR‑γ, TRPC1 and TRPC6 affect the development of vascular remodeling in PPHN model rats remains unknown. The aim of the present study was to investigate the roles of PPAR‑γ, TRPC1 and TRP6 on the pathogenesis of PPHN in rats. The rat model of PPHN was established by exposure to hypoxic conditions and indomethacin treatment. Lung tissues, hearts and blood from PPHN model and Control rats were collected and examined. Parameters, including the percentage of medial wall thickness (WT %), the percentage of medial wall area (WA %), right ventricular hypertrophy (RVH) and the plasma concentration of B‑type natriuretic peptide (BNP) were used to estimate the development of PPHN. The expression levels of PPAR‑γ, TRPC1 and TRPC6 in lung tissues were detected by immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction. Significant increases were observed in the WT %, WA %, RVH and plasma BNP in the PPHN group compare with the Control group (P<0.01). In addition, the mRNA and protein expression levels of PPAR‑γ were markedly downregulated (P<0.05 vs. Control). In the PPHN group, the protein expression levels of TRPC1 and TRPC6 were higher compared to the control group; however, there was no difference in the mRNA expression levels (P>0.05). In conclusion, the present study successfully established a PPHN rat model, and the altered expressions of PPAR‑γ, TRPC1 and TRPC6 in the pulmonary artery located in the lungs of newborn rats with PPHN suggested that these proteins may be important mediators of PPHN.

背景与目标： ：新生儿持续性肺动脉高压（PPHN）是威胁生命的疾病，通常在新生儿重症监护室中观察到。 PPHN的病理特征是肺血管重塑，尤其是肺动脉平滑肌细胞（PASMC）增殖。过氧化物酶体增殖物激活受体γ（PPAR-γ）的表达水平降低，PPAR-γ是核受体激素超家族的成员，与瞬态受体潜在阳离子通道，亚家族C，成员1（TRPC1）和TRPC6的表达升高有关对成人肺动脉高压（PH）中PASMC增殖和过度肺血管重构的影响。 PPAR-γ，TRPC1和TRPC6是否影响PPHN模型大鼠血管重塑的发展尚不清楚。本研究的目的是研究PPAR-γ，TRPC1和TRP6在大鼠PPHN发病中的作用。通过暴露于低氧条件和消炎痛治疗，建立了PPHN大鼠模型。收集并检查PPHN模型和对照组大鼠的肺组织，心脏和血液。使用参数，包括内侧壁厚百分比（WT％），内侧壁面积百分比（WA％），右心室肥大（RVH）和B型利钠肽（BNP）的血浆浓度来评估发育情况PPHN。通过免疫组织化学，Western印迹和逆转录定量聚合酶链反应检测肺组织中PPAR‑γ，TRPC1和TRPC6的表达水平。与对照组相比，PPHN组的WT％，WA％，RVH和血浆BNP显着增加（P <0.01）。此外，PPAR-γ的mRNA和蛋白表达水平显着下调（P <0.05 vs.Control）。 PPHN组的TRPC1和TRPC6的蛋白表达水平高于对照组。然而，mRNA表达水平没有差异（P> 0.05）。总之，本研究成功建立了PPHN大鼠模型，而PPHN新生大鼠肺中肺动脉中PPAR-γ，TRPC1和TRPC6的表达改变表明，这些蛋白可能是PPHN的重要介体。

BACKGROUND & AIMS: BACKGROUND:Recent air travel recommendations suggest patients with precapillary pulmonary hypertension (PCPH) in New York Heart Association (NYHA) functional class 3 and 4 should have in-flight oxygen without the need for pre-flight testing. However it remains unclear as to how best to determine patients fitness to fly. METHODS:This study (i) investigates the effect of hypoxic challenge testing (HCT) on the arterial oxygen levels in a cohort of 36 patients with PCPH and (ii) compares the relative frequency with which FC and HCT predict the requirement for in-flight oxygen. RESULTS:The degree of arterial hypoxaemia induced by HCT (fall in partial pressure of oxygen in arterial blood (PaO(2)) 2.36 kPa, 95% CI 2.06-2.66 kPa) was similar to the drop observed in other published studies of chronic respiratory diseases. Following current air travel recommendations based on FC, 25 patients of the cohort would require in-flight oxygen whilst 10 subjects failed the HCT. Fourteen subjects had flown post-diagnosis. Of these, nine subjects should have had in-flight oxygen based on FC but were asymptomatic without. Also one who passed the HCT had developed symptoms during the flight whilst three who failed the HCT were asymptomatic flying without in-flight oxygen. CONCLUSIONS:Hypoxaemia induced by simulated air travel in patients with PCPH is similar to that seen in published studies of patients with other chronic respiratory diseases. HCT failed to predict correctly who had developed symptoms during an aircraft flight in a significant minority of the study subjects. Similarly guidelines based on functional class result in a major increase in the proportion of patients being advised to use oxygen, many of whom had been asymptomatic on previous flights without it. More work is required to improve prediction of need for in-flight oxygen in patients with PCPH.

背景与目标： 背景：最近的航空旅行建议建议，纽约心脏协会（NYHA）功能3级和4级的毛细血管前肺动脉高压（PCPH）患者应在飞行中进行氧气测试，而无需进行飞行前测试。然而，如何最好地确定患者是否适合飞行尚无定论。
方法：这项研究（i）研究了36例PCPH患者的低氧激发试验（HCT）对动脉血氧水平的影响，并且（ii）比较了FC和HCT预测机上需求的相对频率氧。
结果：HCT引起的动脉低氧血症程度（动脉血中的氧分压下降（PaO（2））2.36 kPa，95％CI 2.06-2.66 kPa）与在其他已发表的慢性呼吸道研究中观察到的下降相似疾病。根据当前基于FC的航空旅行建议，该队列中的25名患者需要机上氧气，而10名HCT失败。 14名受试者进行了飞行后诊断。其中，九名受试者应基于FC接受机上氧气，但无症状则无症状。另外，通过HCT的一名飞行员在飞行过程中出现了症状，而三名未通过HCT的飞行员则是在没有机上氧气的情况下无症状飞行。
结论：PCPH患者模拟航空旅行引起的低氧血症与发表于其他慢性呼吸道疾病患者的研究相似。 HCT无法正确预测在少数研究对象中谁在飞机飞行期间出现症状。类似地，基于功能舱的指南导致建议使用氧气的患者比例大大增加，其中许多人在以前的航班中没有氧气就无症状。需要做更多的工作来改善PCPH患者机内氧气需求的预测。

BACKGROUND & AIMS: :Device-based antihypertensive treatments have primarily been developed and clinically tested for patients with hypertension refractory to pharmacological treatment. Most but not all device-based treatments target the sympathetic nervous system and provided important new insight in the mechanisms of human hypertension. This review provides an overview on the scientific rational and clinical data on recent device-based antihypertensive treatment approaches. Device-based treatments targeting the sympathetic nervous system include catheter-based renal nerve ablation, electrical carotid sinus stimulation, modulation of baroreflex transduction through a dedicated carotid stent, carotid body denervation, and deep brain stimulation. Creation of a defined arteriovenous stent with a coupler device and removal of stimulatory antibodies against alpha adrenoreceptors have also been tested. The clinical evidence differs from therapy to therapy with the largest dataset for renal nerve ablation followed by electrical carotid sinus stimulation. Yet, none has been proven efficacious in sham-controlled clinical trials, and none has been shown to reduce cardiovascular morbidity or mortality. Before efficacy is proven, these treatments should not be part of routine medical care and only be applied in the setting of clinical studies.

背景与目标： ：基于器械的降压治疗已被初步开发，并针对药物治疗难以治疗的高血压患者进行了临床测试。大多数但不是全部基于设备的治疗均针对交感神经系统，并为人类高血压的机制提供了重要的新见解。这篇综述提供了关于基于设备的抗高血压治疗方法的科学合理性和临床数据的概述。针对交感神经系统的基于设备的治疗包括基于导管的肾神经消融，颈动脉窦电刺激，通过专用颈动脉支架调节压力反射反射，颈动脉去神经支配和深部脑刺激。还已经测试了具有耦合器的限定的动静脉支架的创建以及针对α肾上腺素能受体的刺激性抗体的去除。每种疗法的临床证据各不相同，其中最大的肾神经消融数据集随后是颈动脉窦电刺激疗法。然而，没有任何一种药物在假对照临床试验中被证明是有效的，并且没有一种药物能够降低心血管疾病的发病率或死亡率。在证明疗效之前，这些治疗方法不应成为常规医疗服务的一部分，而只能用于临床研究。

BACKGROUND & AIMS: :We performed a retrospective cohort analysis of pregnancies among women with moderate to complex congenital heart disease or pulmonary hypertension over a 12-year period, resulting in a cohort of 107 cases in 65 women. Neuraxial analgesia or anaesthesia was provided in 84%, 89% and 95% of spontaneous vaginal, operative vaginal and caesarean deliveries, respectively. The caesarean delivery rate was 43% compared to our institution average of 27% over the same period (p = 0.02), and 38% had operative vaginal deliveries compared to a 10.5% institution rate (p < 0.01). Invasive monitoring was used in 28% of all deliveries. There were one maternal and two neonatal deaths. This study provides detailed anaesthetic and peripartum management of women with congenital heart disease, a patient population in whom evidence-based practice and data are largely lacking. We observed a predominance of neuraxial anaesthetic techniques, increased caesarean and operative delivery rates, and favourable maternal and neonatal outcomes. Multicentre studies and registries to compare anaesthetic and obstetric management strategies further and delineate risk factors for adverse outcomes are required.

背景与目标： ：我们对12年来中度至复杂先天性心脏病或肺动脉高压妇女的妊娠进行了回顾性队列研究，结果65例妇女中有107例队列。自发性阴道，手术性阴道和剖宫产分别有84％，89％和95％提供神经镇痛或麻醉作用。剖腹产率为43％，而同期我们机构的平均水平为27％（p = 0.02），而手术阴道分娩的比例为38％，而机构率为10.5％（p <0.01）。在所有分娩中有28％使用了侵入式监测。有1名孕产妇死亡和2名新生儿死亡。这项研究为患有先天性心脏病的妇女提供了详细的麻醉和围产期治疗方法，该病患者中大量缺乏循证医学实践和数据。我们观察到神经麻醉技术占优势，剖腹产和手术分娩率增加，孕产妇和新生儿预后良好。需要进行多中心研究和登记，以进一步比较麻醉和产科管理策略，并描述不良后果的危险因素。

BACKGROUND & AIMS: :Leptin (a neuroendocrine peptide that enhances metabolism and acts on the hypothalamus to suppress appetite) and adiponectin (a protein that has insulin-sensitizing, anti-inflammatory, and antiproliferative properties) are involved in the pathobiology of pulmonary arterial hypertension (PAH). We hypothesized that plasma leptin and adiponectin as well as the leptin/adiponectin ratio are abnormal in PAH patients and their levels track with disease severity and functional changes during follow-up. We tested this hypothesis in a cohort of patients included in the 16-week, international, multicenter, double-blind, placebo-controlled FREEDOM-C2 study. Blood was collected at baseline and week 16 in 178 out of 310 randomized patients with PAH. Baseline plasma leptin and adiponectin concentrations were 25 ± 31 ng/mL and 7.8 ± 6.1 ug/mL, respectively. Leptin, adiponectin, and leptin/adiponectin (mean ± SD) changes at 16 week were of small magnitude. Leptin at baseline was significantly associated with older age, higher BMI, higher Borg dyspnea index, and lower NT-pro BNP. Women had higher levels of leptin than men (30.5 ± 33.2 versus 7.2 ± 6.4 ng/mL), even when adjusting for background therapy and etiology (linear regression: β = 21.8, P < 0.001). Adiponectin was negatively associated with BMI and positively associated with NT-pro BNP. Changes in leptin, adiponectin, and leptin/adiponectin ratio adjusted for weight at 16 weeks did not predict functional class, distance walk in 6 min or survival at one, two, three, or four years. Plasma leptin and adiponectin at baseline and their change at 16-week do not appear to significantly impact prognosis in PAH.

背景与目标： ：瘦素（一种增强神经代谢的神经内分泌肽，作用于下丘脑以抑制食欲）和脂连蛋白（一种具有胰岛素敏感性，抗炎和抗增殖特性的蛋白质）参与了肺动脉高压（PAH）的病理生物学研究。我们假设PAH患者的血浆瘦素和脂联素以及瘦素/脂联素比值异常，并且其水平随随访期间的疾病严重程度和功能变化而变化。我们在16周，国际，多中心，双盲，安慰剂对照的FREEDOM-C2研究中对一组患者进行了检验。在310位随机分组的PAH患者中，有178位在基线和第16周采集了血液。基线血浆瘦素和脂联素浓度分别为25±±31μng/ mL和7.8±±6.1μg/ mL。瘦素，脂联素和瘦素/脂联素在16周时的变化很小。基线时的瘦素与年龄增加，BMI升高，Borg呼吸困难指数升高和NT-pro BNP降低显着相关。即使调整背景治疗和病因，女性的瘦素水平也比男性高（30.5±33.2 vs 7.2±6.4μng/ mL）（线性回归：β≥21.8，P <0.001）。脂联素与BMI负相关，与NT-pro BNP正相关。瘦体重，脂联素和瘦素/脂联素之比的变化（按体重在16周时调整）不能预测功能等级，6分钟步行距离或一，二，三年或四年的生存率。基线时血浆瘦素和脂联素及其在16周时的变化似乎并未显着影响PAH的预后。

BACKGROUND & AIMS: We determined functional and morphological changes of the heart by 2-dimensional and pulse Doppler echocardiography in 20 patients with primary aldosteronism and compared the results with those in 50 healthy normotensive subjects, 12 patients with Cushing's syndrome, 9 patients with pheochromocytoma, and 47 patients with essential hypertension. All hypertensive groups had greater left ventricular mass indexes than did the normotensive group (76.9 +/- 17.2 g/m2). Despite similar age distribution, blood pressure during antihypertensive treatment, and duration of hypertension, the primary aldosteronism group had a significantly greater left ventricular mass index (152.5 +/- 42.5 g/m2) than did the Cushing's syndrome (103.4 +/- 37.5 g/m2), pheochromocytoma (122.4 +/- 28.5 g/m2), and essential hypertension (101.4 +/- 32.8 g/m2) groups. The left ventricular posterior wall thickness and interventricular septal wall thickness were significantly greater in the hypertensive groups than in the normotensive group and also significantly greater in the primary aldosteronism group than in any of the other hypertensive groups. By contrast, there were no significant differences among the four hypertensive groups in any variable of systolic or diastolic function of the heart. The results suggest that left ventricular hypertrophy is more pronounced in patients with primary aldosteronism than in patients with other forms of hypertension. It is therefore important to echocardiographically evaluate cardiac hypertrophy as a risk factor of morbidity and mortality in patients with this low renin hypertension.

背景与目标： 我们通过二维和脉冲多普勒超声心动图确定了20例原发性醛固酮增多症患者的心脏功能和形态变化，并将结果与​​50例健康血压正常的受试者，12例库欣综合症，9例嗜铬细胞瘤和47例原发性高血压。所有高血压组的左心室质量指数均高于正常血压组（76.9 / 17.2 g / m2）。尽管年龄分布，抗高血压治疗期间的血压以及高血压持续时间相近，但原发性醛固酮增多症组的左心室质量指数（152.5 /-42.5 g / m2）明显高于库欣综合征（103.4 /-37.5 g / m2） ），嗜铬细胞瘤（122.4 /-28.5 g / m2）和原发性高血压（101.4 /-32.8 g / m2）组。高血压组的左心室后壁厚度和室间隔间隔壁厚度显着大于正常血压组，而原发性醛固酮增多症组也显着大于其他任何高血压组。相比之下，在四个高血压组之间，心脏的任何收缩或舒张功能变量均无显着差异。结果表明，原发性醛固酮增多症患者比其他形式的高血压患者左室肥厚更为明显。因此，超声心动图评估心脏肥大是低肾素高血压患者发病和死亡的危险因素，这一点很重要。

BACKGROUND & AIMS: :By interrupting the integrity of the systemic and renal renin-angiotensin system, angiotensin-converting enzyme inhibitors have been shown, experimentally, to preferentially reduce postglomerular capillary arteriolar resistance, to reduce glomerular capillary pressure, and to increase the ultrafiltration coefficient. Under normal physiological conditions, angiotensin-converting enzyme inhibitors have little effect on glomerular filtration rate; however, they increase effective renal plasma flow at renal perfusion pressures within the normal autoregulatory range and renal vascular resistance is decreased. In contrast, calcium antagonists have been shown, experimentally, to preferentially reduce preglomerular capillary arteriolar resistance. Their effects on angiotensin II and postglomerular capillary arteriolar resistance (hence, glomerular capillary pressure and the ultrafiltration coefficient) are controversial. Under normal physiological conditions, calcium antagonists increase both glomerular filtration rate and effective renal plasma flow at renal perfusion pressures within the normal autoregulatory range and renal vascular resistance is decreased. In patients with essential hypertension, studies have demonstrated that angiotensin-converting enzyme inhibitors (as predicted) sustain glomerular filtration rate, increase effective renal plasma flow, and decrease renal vascular resistance. However, essential hypertensive patients with impaired glomerular filtration rate may demonstrate marked improvement in both glomerular filtration rate and effective renal plasma flow. Calcium antagonists (as predicted) may increase both glomerular filtration rate and effective renal plasma flow (at high renal perfusion pressures) and may decrease renal vascular resistance. Calcium antagonists may also improve both glomerular filtration rate and effective renal plasma flow in patients with impaired glomerular filtration rate. Long-term clinical trials comparing the renal effects of angiotensin-converting enzyme inhibitors with those of calcium antagonists in essential hypertensive patients have not been reported. It remains to be determined if the potentially different effects of these two classes of antihypertensive drugs on the renal microcirculation do or do not translate into different renal protective advantages to patients at risk for the development and/or progression of hypertensive nephrosclerosis.

背景与目标： 通过实验证明，通过破坏全身和肾脏的肾素-血管紧张素系统的完整性，血管紧张素转化酶抑制剂可优先降低肾小球毛细血管小动脉阻力，降低肾小球毛细血管压力，并增加超滤系数。在正常的生理条件下，血管紧张素转化酶抑制剂对肾小球滤过率的影响很小。但是，它们在正常自我调节范围内的肾脏灌注压力下会增加有效的肾脏血浆流量，并且肾血管阻力降低。相反，实验表明，钙拮抗剂可优先降低肾小球前毛细血管的阻力。它们对血管紧张素II和肾小球后毛细血管小动脉阻力（因此，肾小球毛细血管压力和超滤系数）的影响是有争议的。在正常生理条件下，钙拮抗剂在正常自动调节范围内的肾脏灌注压力下会增加肾小球滤过率和有效肾血浆流量，并且肾血管阻力降低。在原发性高血压患者中，研究表明，血管紧张素转化酶抑制剂（如预期的那样）可维持肾小球滤过率，增加有效肾血浆流量并降低肾血管阻力。然而，肾小球滤过率受损的原发性高血压患者可能表现出肾小球滤过率和有效肾血浆流量的明显改善。钙拮抗剂（如预期的那样）可能会增加肾小球滤过率和有效的肾血浆流量（在高肾灌注压力下），并且可能会降低肾血管阻力。对于肾小球滤过率受损的患者，钙拮抗剂还可以改善肾小球滤过率和有效的肾血浆流量。尚未有长期临床试验比较血管紧张素转化酶抑制剂与钙拮抗剂在基本高血压患者中的肾脏作用。这两类降压药对肾脏微循环的潜在不同作用是否会转化为对患有高血压肾硬化发展和/或进展风险的患者的不同肾脏保护优势，尚待确定。

BACKGROUND & AIMS: :Inappropriate activation of the intrarenal renin-angiotensin system induces generation of reactive oxygen species and tubulointerstitial inflammation, which contribute to salt-sensitive hypertension (SSHT). Liver-type fatty acid-binding protein is expressed in proximal tubules in humans, but not in rodents, and may play an endogenous antioxidative role. The objective of the present study was to examine the antioxidative effect of liver-type fatty acid-binding protein on post-angiotensin II SSHT model in transgenic mice with selective overexpression of human liver-type fatty acid-binding protein in the proximal tubules. The transgenic mice showed marked protection against angiotensin II-induced SSHT. Overexpression of tubular liver-type fatty acid-binding protein prevented intrarenal T-cell infiltration and also reduced reactive oxygen species generation, intrarenal renin-angiotensin system activation, and monocyte chemotactic protein-1 expression. We also performed an in vitro study using the murine proximal tubular cell lines with or without recombinant liver-type fatty acid-binding protein and murine proximal tubular cell lines transfected with human liver-type fatty acid-binding protein, and found that gene transfection of liver-type fatty acid-binding protein and, in part, recombinant liver-type fatty acid-binding protein administration had significantly attenuated angiotensin II-induced reactive oxygen species generation and the expression of angiotensinogen and monocyte chemotactic protein-1 in murine proximal tubular cell lines. These findings indicated that liver-type fatty acid-binding protein in the proximal tubules may protect against angiotensin II-induced SSHT by attenuating activation of the intrarenal renin-angiotensin system and reducing oxidative stress and tubulointerstitial inflammation. Present data suggest that liver-type fatty acid-binding protein in the proximal tubules may be a novel therapeutic target for SSHT.

背景与目标： ：肾内肾素-血管紧张素系统的不适当活化会诱导活性氧的产生和肾小管间质发炎，从而导致盐敏感性高血压（SSHT）。肝型脂肪酸结合蛋白在人的近端小管中表达，但在啮齿动物中不表达，并且可能起内源性抗氧化作用。本研究的目的是研究肝型脂肪酸结合蛋白对在近端小管中选择性表达人肝型脂肪酸结合蛋白的转基因小鼠中血管紧张素ⅡSSHT模型的抗氧化作用。转基因小鼠对血管紧张素II诱导的SSHT具有明显的保护作用。肾小管型脂肪酸结合蛋白的过度表达阻止了肾内T细胞的浸润，并减少了活性氧的产生，肾内肾素-血管紧张素系统的活化以及单核细胞趋化蛋白1的表达。我们还使用有或没有重组肝型脂肪酸结合蛋白的鼠近端肾小管细胞系以及用人肝型脂肪酸结合蛋白转染的鼠近端肾小管细胞系进行了体外研究，发现肝型脂肪酸结合蛋白，以及部分重组肝型脂肪酸结合蛋白的给药，显着减弱了血管紧张素II诱导的活性氧的产生以及鼠近端肾小管细胞中血管紧张素原和单核细胞趋化蛋白1的表达线。这些发现表明，近端小管中的肝型脂肪酸结合蛋白可通过减弱肾内肾素-血管紧张素系统的激活并减少氧化应激和肾小管间质炎症来预防血管紧张素II诱导的SSHT。目前的数据表明，近端肾小管中的肝型脂肪酸结合蛋白可能是SSHT的新型治疗靶标。

BACKGROUND & AIMS: :Chronic administration of nadolol has been reported to reduce blood pressure either without or with a concomitant fall of renal blood flow. We therefore studied the effects of nadolol 80 mg once daily on ambulatory blood pressure, renal and systemic haemodynamics in patients with mild to moderate essential hypertension. Ten patients took part in this randomized, double-blind, placebo-controlled, crossover study, each phase of which lasted 4 weeks. Nadolol significantly reduced ambulatory blood pressure and heart rate, but had no effect on blood pressure variability. Cardiac output was significantly reduced by nadolol and total peripheral resistance increased but without reaching statistical significance. Despite the fall in blood pressure and cardiac output, renal blood flow and glomerular filtration rate remained unchanged. The fraction of cardiac output reaching the kidneys rose significantly and renal vascular resistance was significantly reduced. Body weight, urinary sodium excretion and urine flow rate remained unchanged. We conclude that nadolol 80 mg once daily lowers ambulatory blood pressure in patients with mild to moderate hypertension without impairment of renal blood flow, indicating a redistribution of cardiac output to the kidneys. The mechanism of the renal vasodilator effect of nadolol remains to be determined.

背景与目标： ：有报道称，长期服用萘多洛可降低血压，既不伴有肾血流下降，也可伴有肾血流下降。因此，我们研究了纳多洛尔80 mg每天一次对轻度至中度原发性高血压患者动态血压，肾脏和全身血流动力学的影响。十名患者参加了这项随机，双盲，安慰剂对照，交叉研究，其每个阶段持续4周。纳多洛尔显着降低了门诊血压和心率，但对血压变异性没有影响。萘多洛尔可显着降低心输出量，总外周阻力增加，但未达到统计学意义。尽管血压和心输出量下降，但肾血流量和肾小球滤过率保持不变。到达肾脏的心输出量比例显着上升，肾血管阻力显着降低。体重，尿钠排泄和尿流率保持不变。我们得出的结论是，纳多洛尔80 mg每天一次可降低轻度至中度高血压患者的门诊血压，而不会损害肾血流量，这表明心输出量会重新分配给肾脏。纳多洛尔的肾血管舒张作用机制尚待确定。

BACKGROUND & AIMS: :Pulmonary hypertension (PH) associated with pulmonary fibrosis (PF) considerably worsens prognosis of interstitial lung diseases (ILD). RhoA/Rho-kinases (ROCK) pathway is implicated in high pulmonary vascular tone and pulmonary fibrosis but the effect of ROCK inhibitors on PH associated with PF is not known. We therefore aimed to determine whether long-term treatment with fasudil, a selective ROCK inhibitor, could attenuate PF and PH induced by bleomycin in mice. Male C57BL/6 mice received a single dose of intratracheal bleomycin (3.3 U/kg) to induce PF. Treatment with fasudil (30 mg kg(-1) day(-1)) was given intraperitoneally for 7, 14 or 21 days until mice underwent hemodynamic measurements. Right ventricular systolic pressure (RVSP) and RV/(LV + S) ratio were assessed. Lung inflammatory cells profiles, including macrophages, neutrophils, lymphocytes B and lymphocytes T were assessed by immunohistochemistry. Lung fibrosis was evaluated by histological and biochemical methods. Pulmonary arteriole muscularization and medial wall thickness (MWT) were evaluated by immunohistochemical staining for α-SMA. Bleomycin induced severe PF and PH in mice, associated with an increased RhoA/ROCK activity in the lung. Fasudil reduced lung inflammation and lung collagen content, and attenuated the increased RVSP, RV hypertrophy, and pulmonary vascular remodeling in bleomycin-intoxicated mice. Fasudil inhibited the increased activity of RhoA/ROCK pathway, and partly altered bleomycin-associated activation of TGF-β1/Smad pathway, via inhibition of Smad2/3 phosphorylation. The efficacy of long-term treatment with fasudil suggests that the blockade of RhoA/ROCK pathway may be a promising therapy for patients with ILD-associated PH.

背景与目标： ：与肺纤维化（PF）相关的肺动脉高压（PH）大大恶化了间质性肺疾病（ILD）的预后。 RhoA / Rho激酶（ROCK）通路与高肺血管张力和肺纤维化有关，但尚不清楚ROCK抑制剂对与PF相关的PH的影响。因此，我们旨在确定长期用选择性ROCK抑制剂法舒地尔治疗是否能减弱博来霉素诱导的小鼠的PF和PH。雄性C57BL / 6小鼠接受单剂量气管内博来霉素（3.3 U / kg）诱导PF。腹腔内给予法舒地尔（30 mg kg（-1）day（-1））治疗7、14或21天，直到小鼠接受血液动力学测量。评估右心室收缩压（RVSP）和RV /（LV S）比。通过免疫组织化学评估肺炎性细胞概况，包括巨噬细胞，嗜中性粒细胞，淋巴细胞B和淋巴细胞T。通过组织学和生化方法评估肺纤维化。通过免疫组织化学染色对α-SMA评估肺小动脉肌肉化和内侧壁厚度（MWT）。博来霉素诱导小鼠中严重的PF和PH，与肺中RhoA / ROCK活性增加有关。 Fasudil减少了博来霉素中毒小鼠的肺部炎症和肺胶原含量，并减轻了RVSP，RV肥大和肺血管重塑。 Fasudil通过抑制Smad2 / 3磷酸化来抑制RhoA / ROCK途径的活性增加，并部分改变与博莱霉素相关的TGF-β1/ Smad途径的活化。法舒地尔的长期治疗效果表明，RhoA / ROCK通路的阻断对于ILD相关性PH患者可能是一种有前途的治疗方法。

BACKGROUND & AIMS: :This review describes effects of miso with reference to prevention of radiation injury, cancer and hypertension with a twin focus on epidemiological and experimental evidence. Miso with a longer fermentation time increased crypt survival against radiation injury in mice. When evaluating different types of miso provided by different areas in Japan, miso fermented for a longer period increased the number of surviving crypts, and 180 days of fermentation was the most significant. Dietary administration of 180-day fermented miso inhibits the development of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and rat colon cancers in F344 rats. Miso was also effective in suppression of lung tumors, breast tumors in rats and liver tumors in mice. The incidence of gastric tumors of groups of rats given NaCl was higher than those of the groups given miso fermented for longer periods. Moreover, the systolic blood pressure of the Dahl male rat on 2.3% NaCl was significantly increased but that of the SD rat was not. However, the blood pressures of the rats on a diet of miso or commercial control diet (MF) did not increase. Even though miso contains 2.3% NaCl, their blood pressures were as stable as those of rats fed commercial diet containing 0.3% salt. So we considered that sodium in miso might behave differently compared with NaCl alone. These biological effects might be caused by longer fermentation periods.

背景与目标： ：这篇综述描述了味o在预防放射损伤，癌症和高血压方面的作用，并以流行病学和实验证据为重中之重。具有较长发酵时间的味iso可提高小鼠隐窝抵抗放射损伤的存活率。在评估日本不同地区提供的不同类型的味o时，长时间发酵的味o增加了存活的隐窝的数量，最重要的是发酵180天。饮食中180天发酵味mis的饮食可抑制F344大鼠中乙氧基甲烷（AOM）诱导的异常隐窝灶（ACF）和大鼠结肠癌的发展。味iso在抑制肺肿瘤，大鼠乳腺肿瘤和小鼠肝肿瘤方面也有效。给予NaCl的大鼠胃肿瘤的发生率高于经长期不适当发酵的大鼠的胃肿瘤。此外，Dahl雄性大鼠在2.3％NaCl上的收缩压显着升高，而SD大鼠则没有。但是，以味o饮食或商业对照饮食（MF）饮食的大鼠血压并未增加。即使味o中含有2.3％的氯化钠，它们的血压也与喂食含有0.3％盐的商业饮食的老鼠的血压一样稳定。因此，我们认为味sodium中的钠与单独的NaCl相比可能具有不同的行为。这些生物学效应可能是由更长的发酵时间引起的。

BACKGROUND & AIMS: :High blood pressure (BP) is the most important modifiable risk factor for stroke and other vascular diseases. Evidence from randomized controlled trials supports the use of antihypertensive drugs to lower blood pressure for stroke prevention. There is some evidence that specific classes of antihypertensive drugs have different effects and/or their pharmacological actions differ in patient subgroups. This review evaluates the development of antihypertensive therapies and the latest studies of arterial hypertension and stroke prevention: HOPE trial (ramipril versus placebo), ALLHAT trial (CCB or/ and Angiotensin-Conventing enzyme Inhibitors (ACE-Is) versus diuretic), LIFE trial (losartan versus atenolol), and PROGRESS trial (perindopril or/and indapamide versus placebo). Despite the results of these relevant clinical trails, some aspects still remain unresolved. Future clinical trials on hypertension and stroke prevention should answer the following questions: Does lowering BP reduce stroke risk due to specific drug effect or class effect? Are angiotensin II receptor blockers (ARBs) better than ACE-Is? Should ACE-Is and ARBs be considered routinely for either high-risk stroke patients or patients with history of stroke or transient ischemic attack, irrespective of blood pressure? What is the role of lifestyle in BP control?

背景与目标： ：高血压（BP）是中风和其他血管疾病的最重要的可改变危险因素。随机对照试验的证据支持使用降压药降低血压以预防中风。有证据表明，特定类别的降压药在患者亚组中具有不同的作用和/或它们的药理作用。这篇综述评估了抗高血压疗法的发展以及动脉高血压和中风预防的最新研究：HOPE试验（雷米普利与安慰剂），ALLHAT试验（CCB或/和血管紧张素抑制酶抑制剂（ACE-Is）与利尿剂），LIFE试验（氯沙坦vs阿替洛尔）和PROGRESS试验（培哚普利或/和吲达帕胺vs安慰剂）。尽管取得了这些相关临床试验的结果，但仍未解决某些方面。未来有关高血压和中风预防的临床试验应回答以下问题：降低BP是否会由于特定的药物作用或类别作用而降低中风风险？血管紧张素II受体阻滞剂（ARB）是否比ACE-Is好？对于高危中风患者或有中风病史或短暂性脑缺血发作的患者，无论血压高低，均应常规考虑使用ACE-Is和ARB吗？生活方式在血压控制中的作用是什么？

BACKGROUND & AIMS: :We examined whether maternal educational level as an indicator of socioeconomic status is associated with gestational hypertension. We also examined the extent to which the effect of education is mediated by maternal substance use (that is smoking, alcohol consumption and illegal drug use), pre-existing diabetes, anthropometrics (that is height and body mass index (BMI)) and blood pressure at enrollment. This was studied in 3262 Dutch pregnant women participating in the Generation R Study, a population-based cohort study. Level of maternal education was established by questionnaire at enrollment, and categorized into high, mid-high, mid-low and low. Diagnosis of gestational hypertension was retrieved from medical records using standard criteria. Odds ratios (OR) of gestational hypertension for educational levels were calculated, adjusted for potential confounders and additionally adjusted for potential mediators. Adjusted for age and gravidity, women with mid-low (OR: 1.52; 95% CI: 1.02, 2.27) and low education (OR: 1.30; 95% CI: 0.80, 2.12) had a higher risk of gestational hypertension than women with high education. Additional adjustment for substance use, pre-existing diabetes, anthropometrics and blood pressure at enrollment attenuated these ORs to 1.09 (95% CI: 0.70, 1.69) and 0.89 (95% CI: 0.50, 1.58), respectively. These attenuations were largely due to the effects of BMI and blood pressure at enrollment. Women with relatively low educational levels have a higher risk of gestational hypertension, which is largely due to higher BMI and blood pressure levels from early pregnancy. The higher risk of gestational hypertension in these women is probably caused by pre-existing hypertensive tendencies that manifested themselves during pregnancy.

背景与目标： ：我们研究了孕产妇受教育程度作为社会经济地位的指标是否与妊娠高血压相关。我们还研究了母体物质使用（即吸烟，饮酒和非法使用毒品），先前存在的糖尿病，人体测量学（即身高和体重指数（BMI））和血液对教育效果的影响程度入学压力。这项针对基于人群的队列研究“ Generation R Study”参与了3262名荷兰孕妇的研究。入学时通过问卷调查确定孕产妇教育水平，并将其分为高，中高，中低和低。使用标准标准从病历中检索出妊娠高血压的诊断。计算了受教育程度的妊娠高血压的赔率（OR），针对潜在的混杂因素进行了调整，此外还针对潜在的调解人进行了调整。经过年龄和妊娠度调整后，中低（OR：1.52； 95％CI：1.02、2.27）和低学历（OR：1.30； 95％CI：0.80、2.12）的妇女比患有HLA的女性发生妊娠高血压的风险更高高等教育。入组时对药物使用，先前存在的糖尿病，人体测量学和血压的其他调整分别将这些OR衰减至1.09（95％CI：0.70、1.69）和0.89（95％CI：0.50、1.58）。这些衰减主要归因于入学时的BMI和血压的影响。受教育程度相对较低的妇女发生妊娠高血压的风险较高，这在很大程度上是由于早孕期的BMI和血压水平较高。这些妇女的妊娠高血压风险较高，可能是由于怀孕期间已存在的高血压倾向所致。