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。

BACKGROUND & AIMS: :This study aims to decipher the potential effects of nebivolol in prevention and/or regression of renal artery dysfunction in diabetes associated with hypertension. Renal arteries were isolated from 80 male mice divided into four experimental groups: (i) group D: diabetics, at 2 months since streptozotocin injection; (ii) group Din: mice that at the initiation of streptozotocin diabetes were treated with 10 mg/kg b.w./day nebivolol for 2 months, to test for the potential prevention of vascular dysfunction; (iii) group Dfin: mice that after 2 months of diabetes were treated daily with 10 mg/kg b.w./day nebivolol for additional 2 months, in order to follow the possible regression of the dysfunction, and (iv) controls (C), age-matched healthy animals. The following measurements were performed: arterial blood pressure, plasma glucose concentration, and the vascular reactivity of the renal arteries in response to noradrenaline (10(-4) M), acetylcholine (10(-4) M) and sodium nitroprusside (10(-4) M). To assess the molecular mechanisms involved in the reactivity of the renal artery, the contribution of mitogen-activated protein kinase (MAP kinase) pathway and of L-type voltage gated Ca(2+) channels (in the contractile response to noradrenaline), of nitric oxide (NO) and Ca(2+) activated K(+) channels (in the endothelium-dependent vasodilator response), and of cGMP (in the endothelium-independent vasodilator response) was examined by exposing the arteries to corresponding inhibitors, and by using myograph and patch-clamp techniques, immunoblotting and NO assays. Results showed that, group D was characterized by hyperglycemia (blood glucose concentration: 136.66 +/- 4.96 mg/dl, a value approximately 65% increased compared to group C) and hypertension (systolic blood pressure: 145.66 +/- 5.96 mm Hg, a value approximately 34% increased compared to group C). Compared to group D, group Din was characterized by diminished blood glucose concentration ( approximately 1.6 fold), reduced systolic and diastolic blood pressure ( approximately 1.3 fold) and heart rate ( approximately 1.6 fold), as well as by increased contractile response of the renal artery to noradrenaline ( approximately 1.84 fold) and of the impeded vasodilator response to acetylcholine ( approximately 1.81 fold) and sodium nitroprusside ( approximately 1.42 fold). Together, these effects demonstrate that administration of 10 mg/kg b.w./day nebivolol at the moment of diabetes induction has preventive effects, ameliorating diabetes dysfunctions. Compared to group D, group Dfin was characterized by diminished glucose concentration ( approximately 1.3 fold), reduced systolic and diastolic blood pressure and heart rate (both approximately 1.2 fold), and by augmentation of contractile response of the renal artery to noradrenaline ( approximately 1.62 fold) and of vasodilator response to acetylcholine ( approximately 1.13 fold) and sodium nitroprusside ( approximately 1.19 fold). These effects assess that administration of 10 mg/kg b.w./day nebivolol after 2 months of diabetes contributes to regression of diabetes-associated dysfunctionalies. Nebivolol influenced the molecular mechanisms involved in renal artery reactivity in diabetic and hypertensive mice: it increased the NO production and endothelial NO synthase (eNOS) protein expression, decreased the expression of proportional, variant protein in L-type calcium channels and Ca(2+) activated K(+) channels, and diminished the MAP kinase activity. The reported data suggest that nebivolol may offer additional vascular protection for treating diabetes associated with hypertension.

背景与目标： ：本研究旨在阐明奈必洛尔在与高血压相关的糖尿病中预防和/或预防肾动脉功能障碍的潜在作用。从80只雄性小鼠中分离出肾动脉，将其分成四个实验组：（i）D组：糖尿病患者，注射链脲佐菌素后2个月； （ii）Din组：在链脲佐菌素糖尿病开始时的小鼠用10mg / kg体重/天/天的奈必洛尔治疗2个月，以测试潜在的预防血管功能障碍的能力； （iii）Dfin组：在糖尿病2个月后，每天接受10 mg / kg bw /天的奈必洛尔治疗的小鼠再增加2个月，以追踪功能障碍的可能消退；和（iv）对照组（C），年龄匹配的健康动物。进行了以下测量：动​​脉血压，血浆葡萄糖浓度和响应去甲肾上腺素（10（-4）M），乙酰胆碱（10（-4）M）和硝普钠（10（ -4）M）。若要评估参与肾动脉反应性，丝裂原活化蛋白激酶（MAP激酶）途径和L型电压门控Ca（2）通道（在对去甲肾上腺素的收缩反应中）的贡献的分子机制，硝酸通过将动脉暴露于相应的抑制剂并通过使用肌电描记器来检查氧化物（NO）和Ca（2）激活的K（）通道（在内皮依赖性血管舒张剂反应中）和cGMP（在内皮依赖性血管舒张剂反应中）和膜片钳技术，免疫印迹和NO分析。结果显示，D组的特征是高血糖症（血糖浓度：136.66 /-4.96 mg / dl，与C组相比，升高了约65％）和高血压（收缩压：145.66 /-5.96 mm Hg，与C组相比，约增加了34％。与D组相比，Din组的特征在于血糖浓度降低（约1.6倍），收缩压和舒张压降低（约1.3倍）和心率（约1.6倍），以及肾脏的收缩反应增强到去甲肾上腺素的动脉（约1.84倍）和对乙酰胆碱（约1.81倍）和硝普钠（约1.42倍）的血管舒张反应受阻。这些作用加在一起表明在糖尿病诱发时给予10 mg / kg体重/天的奈必洛尔具有预防作用，可减轻糖尿病的机能障碍。与D组相比，Dfin组的特征在于葡萄糖浓度降低（约1.3倍），收缩压和舒张压和心率降低（均约1.2倍），以及肾动脉对去甲肾上腺素的收缩反应增强（约1.62）倍）和舒张剂对乙酰胆碱（约1.13倍）和硝普钠（约1.19倍）的反应。这些效果评估了糖尿病2个月后给予10 mg / kg b.w./天的奈必洛尔有助于消退与糖尿病相关的功能障碍。 Nebivolol影响了糖尿病和高血压小鼠肾动脉反应的分子机制：它增加了NO的产生和内皮型NO合酶（eNOS）蛋白的表达，降低了L型钙通道和Ca（2）中比例蛋白，变异蛋白的表达。激活K（）通道，并降低MAP激酶活性。报道的数据表明奈必洛尔可能为治疗高血压相关的糖尿病提供额外的血管保护作用。

BACKGROUND & AIMS: STUDY OBJECTIVE:The aim was to clarify the characteristics of the phasic blood velocity pattern and their possible causes in left ventricular hypertrophy secondary to systemic hypertension. DESIGN:Measurements of blood velocities in the left anterior descending coronary artery were made with a 20 MHz Doppler catheter with a top mounted annular crystal. All patients had normal coronary arteriograms. PATIENTS:23 hypertensive patients [systolic/diastolic pressure: 181(SD 15)/100(4) mm Hg)] with left ventricular hypertrophy, and 13 atypical chest pain patients without left ventricular hypertrophy or any abnormal haemodynamic findings (normal controls) entered the study. MEASUREMENTS AND MAIN RESULTS:The left anterior descending coronary artery blood velocity waveform in pressure overloaded left ventricular hypertrophy was characterised by delayed early diastolic inflow. The diastolic rise time of coronary flow (TDR), ie, the time from the beginning of diastole to peak velocity, was higher in patients with hypertensive left ventricular hypertrophy than in normal controls, at 145(56) v 66(15) ms, p less than 0.001. In patients with hypertensive left ventricular hypertrophy, TDR correlated well with the degree of hypertrophy (r = 0.83, p less than 0.01) and also with peak left ventricular systolic pressure (r = 0.62, p less than 0.01). The coronary flow reserve, calculated from the ratio of the diastolic mean velocity after intracoronary injection of papaverine to the resting flow velocity, decreased with prolongation of TDR (r = 0.58, p less than 0.02). CONCLUSIONS:(1) Impairment of early diastolic coronary arterial inflow is the most remarkable characteristic in pressure overloaded left ventricular hypertrophy; (2) preceding systolic vascular compression and impaired left ventricular relaxation correlate with the delayed early diastolic inflow; (3) the delayed inflow is an important possible cause of the decreased coronary flow reserve in the hypertensive left ventricular hypertrophy.

背景与目标： 目的：阐明系统性高血压继发于左心室肥厚的阶段性血流速度特征及其可能原因。
设计：使用20 MHz多普勒导管和顶部安装的环形晶体对冠状动脉左前降支中的血流速度进行测量。所有患者的冠状动脉造影检查均正常。
患者：23例左室肥厚的高血压患者[收缩压/舒张压：181（SD 15）/ 100（4）mm Hg），13例非典型性胸痛患者，无左室肥厚或任何血流动力学异常（正常对照）研究。
测量和主要结果：压力超负荷左心室肥厚中左前降支冠状动脉血流波形的特征是早期舒张期迟发流入。高血压左心室肥厚患者的冠状动脉血流舒张上升时间（TDR），即从舒张开始到达到峰值速度的时间，比正常对照组长，为145（56）v 66（15）ms， p小于0.001。在患有高血压左心室肥大的患者中，TDR与肥大程度（r = 0.83，p小于0.01）以及峰值左心室收缩压（r = 0.62，p小于0.01）密切相关。由冠状动脉内注射罂粟碱后舒张平均速度与静息流速之比计算得出的冠状动脉血流储备随TDR延长而降低（r = 0.58，p小于0.02）。
结论：（1）左心室肥厚是舒张早期冠状动脉血流减少的最显着特征。 （2）收缩期前血管收缩和左心室舒张受损与舒张早期流入延迟有关。 （3）延迟流入是高血压左心室肥厚中冠状动脉血流储备减少的重要可能原因。

BACKGROUND & AIMS: :Animal models of gestational hypertension are problematic. A novel mouse model was described earlier. The dams in that study were transgenic for human angiotensinogen and the sires for human renin; human renin was expressed in and produced by the placenta. This model was adapted to the rat, which has greater utility in terms of chronic instrumentation and physiologic measurements. Female rats transgenic for human angiotensinogen were mated with rats transgenic for human renin. Telemetry BP increased on day 5 of pregnancy from 110/80 mmHg to as high as 180/140 mmHg, while heart rate increased slightly. The renin transgene was expressed in the placenta, which resulted in increased human plasma renin concentration from 0 to 937 +/- 800 ng angiotensin I ml/h; the values returned to 0 after delivery. Female rats transgenic for human renin that were mated with male rats transgenic for human angiotensinogen in contrast exhibited a decrease in BP. In these rats, human angiotensinogen in plasma remained undetectable. Double transgenic offspring of these transgenic rats developed hypertension and end-organ damage, regardless of the source of the transgenes. The conclusion is that transgenic rats that bear human renin and angiotensinogen genes make an attractive model for gestational hypertension. The rat model will have greater utility than the mouse model.

背景与目标： ：妊娠高血压的动物模型是有问题的。较早时描述了一种新颖的小鼠模型。该研究中的大坝是人类血管紧张素原的转基因动物，是人类肾素的父系。人肾素在胎盘中表达并产生。该模型适用于大鼠，在慢性仪器和生理测量方面具有更大的实用性。将针对人血管紧张素原转基因的雌性大鼠与针对人肾素的转基因大鼠交配。妊娠第5天的遥测血压从110/80 mmHg增加到高达180/140 mmHg，而心率则略有增加。肾素转基因在胎盘中表达，导致人血浆肾素浓度从0增加到937 /-800 ng血管紧张素I ml / h；交付后，值将返回0。相比之下，与人类血管紧张素原转基因的雄性大鼠交配的对人类肾素转基因的雌性大鼠表现出BP降低。在这些大鼠中，血浆中的人类血管紧张素原仍然无法检测到。这些转基因大鼠的双转基因后代，无论转基因的来源如何，都患有高血压和终末器官损害。结论是携带人肾素和血管紧张素原基因的转基因大鼠成为妊娠高血压的诱人模型。大鼠模型比小鼠模型具有更大的实用性。

BACKGROUND & AIMS: :Antenatal and postnatal environments are hypothesised to influence the development of hypertension. This study investigates the synergistic effect of cross-fostering and melatonin supplementation on the development of hypertension and renal glutathione system in spontaneously hypertensive rats (SHR). In one experiment, 1-day-old male SHR pups were fostered to either SHR (shr-SHR) or Wistar-Kyoto rats, (shr-WKY). In a concurrent experiment, SHR dams were given melatonin in drinking water (10 mg/kg body weight) from day 1 of pregnancy. Immediately following delivery, 1-day-old male pups were fostered either to SHR (Mel-shr-SHR) or WKY (Mel-shr-WKY) dams receiving melatonin supplementation until weaning on day 21. Upon weaning, melatonin supplementation was continued to these pups until the age of 16 weeks. Systolic blood pressures (SBP) were recorded at the age of 4, 6, 8, 12 and 16 weeks. Renal antioxidant activities were measured. Mean SBP of shr-WKY, Mel-shr-SHR and Mel-shr-WKY was significantly lower than that in shr-SHR until the age of 8 weeks. At 12 and 16 weeks of age, mean SBP of Mel-shr-WKY was lower than those in non-treated shr-SHR and shr-WKY pups but was not significantly different from that in Mel-shr-SHR. Renal glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were significantly higher in Mel-shr-SHR and Mel-shr-WKY at 16 weeks of age. It appears that combination of cross-fostering and melatonin supplementation exerts no synergistic effect on delaying the rise in blood pressure in SHR. The elevated GPx and GST activities are likely to be due to the effect of melatonin supplementation.

背景与目标： ：假设产前和产后环境会影响高血压的发展。这项研究调查了交叉养育和褪黑素补充对自发性高血压大鼠（SHR）高血压和肾脏谷胱甘肽系统发育的协同作用。在一项实验中，将1日龄的雄性SHR幼犬饲养到SHR（shr-SHR）或Wistar-Kyoto大鼠（shr-WKY）中。在一项并行实验中，从怀孕的第一天开始，在SHR大坝中的饮用水中（以体重10 mg / kg体重）给予褪黑激素。分娩后立即将1日龄的雄性幼犬饲养到接受褪黑激素补充的SHR（Mel-shr-SHR）或WKY（Mel-shr-WKY）水坝，直到第21天断奶。断奶后，继续补充褪黑素至这些幼犬直到16周龄。在4、6、8、12和16周龄时记录收缩压（SBP）。测量了肾脏的抗氧化活性。直到8周龄，shr-WKY，Mel-shr-SHR和Mel-shr-WKY的平均SBP均显着低于shr-SHR。在12周和16周龄时，Mel-shr-WKY的平均SBP低于未处理的shr-SHR和shr-WKY幼犬的SBP，但与Mel-shr-SHR的SBP并无显着差异。在16周龄时，Mel-shr-SHR和Mel-shr-WKY的肾脏谷胱甘肽过氧化物酶（GPx）和谷胱甘肽S-转移酶（GST）活性显着更高。似乎交叉培育和褪黑激素补充对延迟SHR血压升高没有协同作用。 GPx和GST活性升高可能是由于补充褪黑激素的影响。