The renin-angiotensin system (RAS) drives vasoconstriction, increased blood pressure and sodium retention in the kidneys, mainly via the action of angiotensin II (Ang II) and its receptor (AT1R). While the system is important for normal kidney function, excessive stimulation of AT1R leads to kidney damage. Angiotensin-(1-7), by contrast, drives vasodilation, reducing blood pressure and kidney damage (a so-called alternative RAS). While boosting Ang-(1-7) to counteract Ang II may seem like a potential treatment strategy for chronic kidney disease (CKD), the situation is complicated by the fact that Ang-(1-7) can actually be derived from Ang II, as well as from other precursors, and it isn’t clear which source of Ang-(1-7) predominates in kidneys. To find out, Kaltenecker and colleagues examined the abundance and activities of RAS and alternative RAS components in healthy and diseased kidney tissue. Using Ang I or Ang II as substrates, the team showed that, in healthy kidneys, Ang-(1-7) is mainly produced from Ang I via the action of an enzyme called neprilysin. In CKD tissue, Ang-(1-7) production is reduced relative to Ang II, the team also showed. These insights into RAS control in the renal system should help guide future therapies for CKD, the authors say.

The chemotherapy drug doxorubicin (DOX) is effective against many types of cancer yet is damaging to the heart. The pathogenesis of DOX-induced cardiomyopathy (DiCM) is largely unknown, but accumulating evidence suggests inflammation, specifically the accumulation of macrophages, plays a critical role. Zhang and colleagues have now investigated the origins and features of cardiac macrophages during DiCM in greater detail. In mice treated with DOX, heart macrophages increased in abundance and originated from both the proliferation of resident cells and recruitment of monocyte-derived macrophages from the circulation, the team showed. These two cell populations differed in their characteristics, with those from the blood being mainly pro-inflammatory and resident cells having a reparative phenotype. The team also found that the resident macrophages exhibited an increased production of the scavenger receptor protein SR-A1 following DOX treatment, and that this receptor promoted the proliferation of the cells. Indeed, in mice lacking SR-A1 the pathology of DiCM was exacerbated. Together the results suggest that boosting the activity of these protective resident macrophages via SR-A1 augmentation may be a route to minimizing heart damage caused by DOX.

Some people faint at the sight of blood or needles, or because they’ve stood up quickly after sitting or lying. Such individuals, who make up approximately one third of the population, have a condition known as vasovagal syncope (VVS)—thought to be caused by sudden drops in both blood pressure and heart rate. Recent evidence suggests a more complicated pre-fainting process, however, with reports that heart volume output is also reduced and that peripheral resistance—a factor affecting blood pressure—can both rise and fall. To determine the precise order and contribution of events prior to fainting, van Dijk and colleagues continuously monitored 163 patients as they underwent a tilt-table-test—a routine method for diagnosing VVS whereby a person’s position is changed from horizontal to upright. Blood pressure, heart output (stroke volume), and heart rate were all continuously assessed while patients were videoed to determine the precise timing of syncope. From averaging the results, the team determined that the initial and predominant contributing factor to fainting is a fall in the heart’s stroke volume, itself probably a result of blood pooling in the lower limbs when the patient is tilted upright. Why such reactions occur in some people and not others, however, was not investigated.

肾素-血管紧张素系统（RAS）主要通过血管紧张素II（Ang II）及其受体（AT1R）的作用来驱动血管收缩，增加血压并在肾脏中保留钠。虽然该系统对于正常的肾功能很重要，但过度刺激AT1R会导致肾脏损害。相比之下，血管紧张素（1-7）驱动血管舒张，降低血压和肾脏损害（所谓的RAS）。虽然增强Ang-（1-7）抵抗Ang II似乎是治疗慢性肾脏疾病（CKD）的潜在策略，但由于Ang-（1-7）实际上可以从Ang II衍生而来的情况使情况变得复杂。以及其他前体，目前尚不清楚肾脏中Ang-（1-7）的主要来源。为了找出答案 Kaltenecker及其同事检查了健康和患病肾脏组织中RAS和其他RAS组分的丰度和活性。研究小组显示，以Ang I或Ang II为底物，在健康的肾脏中，Ang-（1-7）主要是通过一种叫做脑啡肽酶的酶从Ang I产生的。研究小组还显示，在CKD组织中，Ang-（1-7）的产量相对于Ang II减少。这组作者说，这些对肾系统RAS控制的见解应有助于指导CKD的未来治疗。

化疗药物阿霉素（DOX）对多种类型的癌症均有效，但仍会损害心脏。DOX诱发的心肌病（DiCM）的发病机理尚不清楚，但越来越多的证据表明炎症，特别是巨噬细胞的积累起着至关重要的作用。现在，Zhang和同事更详细地研究了DiCM期间心脏巨噬细胞的起源和特征。研究小组显示，在接受DOX处理的小鼠中，心脏巨噬细胞的数量大量增加，并且源自驻留细胞的增殖和循环中单核细胞衍生的巨噬细胞的募集。这两个细胞群的特征不同，血液中的那些主要是促炎性的，而驻留细胞则具有修复的表型。该团队还发现，在DOX处理后，驻留的巨噬细胞显示出清道夫受体蛋白SR-A1的产生增加，并且该受体促进了细胞的增殖。实际上，在缺乏SR-A1的小鼠中，DiCM的病理加剧了。在一起的结果表明，通过SR-A1增强来增强这些保护性常驻巨噬细胞的活性可能是减少DOX引起的心脏损害的途径。

有些人看不见血液或针头，或者因为他们坐下或躺下后很快站起来而晕倒。这些人约占人口的三分之一，患有血管迷走性晕厥（VVS）的状况-认为是由于血压和心率突然下降所致。最近的证据表明，晕厥前的过程更加复杂，有报道说，心脏的容积输出也降低了，外围阻力（影响血压的一个因素）会上升或下降。为了确定晕倒前事件的精确顺序和贡献，van Dijk及其同事对163名患者进行了倾斜表测试，这是诊断VVS的一种常规方法，该方法可将一个人的位置从水平位置更改为垂直位置，从而对其进行连续监测。血压，心输出量（中风量），连续录像评估患者的心律和心率，以确定晕厥的确切时机。通过对结果进行平均，研究小组确定了导致昏厥的最初和主要因素是心脏的中风量下降，这本身可能是患者垂直站立时下肢血液积聚的结果。为什么没有在某些人而不是其他人中发生这种反应的原因。