肾素-血管紧张素-醛固酮系统在高原习服中的作用

目的　探讨肾素 -血管紧张素 -醛固酮系统 (RAAS)在高原低氧习服过程中的作用。方法　将海拔 1 0m处的平原大鼠快速带至海拔 2 2 61m、380 0m的高原地区 ,适应性喂养 48小时 ,取材 ,用放射免疫法 (RIA)测定大鼠血浆PRA、ATⅡ、ALD的浓度。结果　平原大鼠进入高海拔地区后 ,血浆PRA、ATⅡ含量上升 ,ALD含量下降 (P <0 .0 1 )。结论　RAAS在高原习服中参与并发挥着重要作用     

Brain-derived neurotrophic factor and neuron-specific enolase, but not S100β, levels are associated to the occurrence of delirium in intensive care unit patients

Purpose

The aim of this study was to determine the association between serum concentrations of brain-derived neurotrophic factor (BDNF), neuron-specific enolase (NSE), and S100β and the occurrence of delirium in critically ill patients.

Material and Methods

This case-control study included 30 patients with delirium and 30 matched controls in a 16-bed general intensive care unit (ICU). Serum BDNF, NSE, and S100 concentrations were determined by enzyme-linked immunosorbent assay assays at the time of ICU admission and on the day before delirium was diagnosed. Delirium was diagnosed by confusion assessment method for the ICU.

Results

At ICU admission, serum BDNF levels were significantly higher in delirious patients than in nondelirious controls (2.89 ± 1.48 vs 1.79 ± 0.89 ng/mL, respectively). When we compared serum S100 levels, there were no significant differences between the groups. Neuron-specific enolase values were significantly higher in the delirious patients than in the nondelirious controls (0.79 ± 0.03 ng/mL vs 0.59 ± 0.01 ng/mL, respectively). When patients who earlier developed delirium were separately analyzed, it was determined that serum NSE and BDNF levels at admission were significant higher only in this group.

Conclusions

Our results suggest that admission serum BDNF and NSE levels are associated with the occurrence of delirium in ICU patients.     

Portal Hypertension and Related Complications: Diagnosis and Management

Portal hypertension is a major complication of cirrhosis, and its consequences, including ascites, esophageal varices, hepatic encephalopathy, and hepatorenal syndrome, lead to substantial morbidity and mortality. The past several decades have seen major improvements in the clinical management of complications of portal hypertension, resulting in substantial gains in patient outcomes. However, important challenges remain. This review focuses on the pathophysiology and diagnosis of portal hypertension and discusses general approaches in the management of patients with ascites as a result of portal hypertension.     

Renal effects of aspirin are clearly dose-dependent and are of clinical importance from a dose of 160 mg

BACKGROUND: High doses of aspirin counteract the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors. It is not known how low-dose aspirin, with concomitant ACE-inhibitor treatment, affects renal function. AIM: To study renal effects of different doses of aspirin in elderly healthy volunteers who had an activated renin-angiotensin system. METHODS: Sixteen subjects each received two different doses of aspirin (0 and160 mg or 80 and 320 mg) after pre-treatment with bendroflumethiazide and enalapril, in a randomised double-blind, cross-over fashion. RESULTS: Least square means of the observations 30 to 180 min after dosing, showed that urine flow, GFR, excretion rates of sodium, osmolality clearance and free water clearance were significantly decreased in a dose-dependent manner. Urine flow, sodium excretion rate and free water clearance were significantly lower with 320 mg aspirin vs. 0 mg and 80 mg, and GFR was significantly lower with 320 mg vs. 80 mg. Urine flow, sodium excretion rate, free water and osmolality clearance was significantly lower with aspirin 160 mg vs. 0 mg. CONCLUSION: The dose-dependent renal effects of aspirin are of clinical importance from a dose of 160 mg. The adverse influence of aspirin doses higher than 80 mg should be taken into consideration in patients with heart failure.     

Aldosterone: Role in the Cardiometabolic Syndrome and Resistant Hypertension

The prevalence of diabetes, hypertension, and cardiovascular disease (CVD) and chronic kidney disease (CKD) is increasing in concert with obesity. Insulin resistance, metabolic dyslipidemia, central obesity, albuminuria. and hypertension commonly cluster to comprise the cardiometabolic syndrome (CMS). Emerging evidence supports a shift in our understanding of the crucial role of elevated serum aldosterone in promoting insulin resistance and resistant hypertension. Aldosterone enhances tissue generation of oxygen free radicals and systemic inflammation. This increase in oxidative stress and inflammation, in turn, contributes to impaired insulin metabolic signaling, reduced endothelial-mediated vasorelaxation, and associated cardiovascular and renal structural and functional abnormalities. In this context, recent investigation indicates that hyperaldosteronism, which is often associated with obesity, contributes to impaired pancreatic β-cell function as well as diminished skeletal muscle insulin metabolic signaling. Accumulating evidence indicates that the cardiovascular and renal abnormalities associated with insulin resistance are mediated, in part, by aldosterone's nongenomic as well as genomic signaling through the mineralocorticoid receptor (MR). In the CMS, there are increased circulating levels of glucocorticoids, which can also activate MR signaling in cardiovascular, adipose, skeletal muscle, neuronal, and liver tissue. Furthermore, there is increasing evidence that fat tissue produces a lipid soluble factor that stimulates aldosterone production from the adrenal zona glomerulosa. Recently, we have learned that MR blockade improves pancreatic insulin release, insulin-mediated glucose utilization, and endothelium-dependent vasorelaxation as well as reduces the progression of CVD and CKD. In summary, aldosterone excess exerts detrimental metabolic effects that contribute to the development of the CMS and resistant hypertension as well as CVD and CKD.     

Individual variability in response to renin angiotensin aldosterone system inhibition predicts cardiovascular outcome in patients with type 2 diabetes: A primary care cohort study

Aims

To assess variability in systolic blood pressure (SBP) and albuminuria (urinary albumin creatinine ratio [UACR]) responses in patients with type 2 diabetes mellitus initiating renin angiotensin aldosterone system (RAAS) inhibition, and to assess the association of response variability with cardiovascular outcomes.

Material and Methods

We performed an observational cohort study in patients with type 2 diabetes who started RAAS inhibition between 2007 and 2013 (n = 1600). Patients were identified from general practices in the Netherlands. Individual response in SBP and UACR was assessed during 15 months’ follow‐up. Patients were categorized as: good responders (?SBP <0 mm Hg and ?UACR <0%); intermediate responders (?SBP <0 mm Hg and ?UACR >0% or ?SBP >0 mm Hg and ?UACR <0%); or poor responders (?SBP >0 mm Hg and ?UACR >0%). Multivariable Cox regression was performed to test the association between initial RAAS inhibition response and subsequent cardiovascular outcomes.

Results

After starting RAAS inhibition, the mean SBP change was ?13.2 mm Hg and the median UACR was ?36.6%, with large between‐individual variability, both in SBP [5th to 95th percentile: 48.5‐20] and UACR [5th to 95th percentile: ?87.6 to 171.4]. In all, 812 patients (51%) were good responders, 353 (22%) had a good SBP but poor UACR response, 268 (17%) had a good UACR but poor SBP response, and 167 patients (10%) were poor responders. Good responders had a lower risk of cardiovascular events than poor responders (hazard ratio 0.51, 95% confidence interval 0.30‐0.86; P = .012).

Conclusions

SBP and UACR response after RAAS inhibition initiation varied between and within individual patients with type 2 diabetes treated in primary care. Poor responders had the highest risk of cardiovascular events, therefore, more efforts are needed to develop personalized treatment plans for these patients.     

The emerging role of ACE2 in physiology and disease

The renin-angiotensin-aldosterone system (RAAS) is a key regulator of systemic blood pressure and renal function and a key player in renal and cardiovascular disease. However, its (patho)physiological roles and its architecture are more complex than initially anticipated. Novel RAAS components that may add to our understanding have been discovered in recent years. In particular, the human homologue of ACE (ACE2) has added a higher level of complexity to the RAAS. In a short period of time, ACE2 has been cloned, purified, knocked-out, knocked-in; inhibitors have been developed; its 3D structure determined; and new functions have been identified. ACE2 is now implicated in cardiovascular and renal (patho)physiology, diabetes, pregnancy, lung disease and, remarkably, ACE2 serves as a receptor for SARS and NL63 coronaviruses. This review covers available information on the genetic, structural and functional properties of ACE2. Its role in a variety of (patho)physiological conditions and therapeutic options of modulation are discussed.     

Glomerular filtration rate in patients with atrial fibrillation on warfarin treatment: a subgroup analysis from the AURICULA registry in Sweden

Introduction

Numerous associations between chronic kidney disease (CKD) and atrial fibrillation (AF) have been reported and patients with CKD on anticoagulation therapy have an increased risk of bleeding. Currently, new anticoagulant agents are emerging in clinical practice, some of which are excreted by the kidneys. The proportion of AF patients on anticoagulant treatment with reduced renal function is, however, unknown.

Materials and Methods

Using AURICULA, a Swedish registry for anticoagulation, estimated glomerular filtration rate (eGFR) was investigated in AF patients on warfarin treatment (n = 2,603). The study group was compared with a healthy sample from the population (n = 2,261). Two different creatinine prediction equations were used for calculating eGFR: the Lund-Malmö (LM) and MDRD Study equation.

Results

The fraction of AF patients with eGFR < 30 and < 45 ml/min/1.73 m² were 8.1% and 22.9% with the LM and 4.3% and 16.3% with the MDRD equation, respectively, and significantly higher than corresponding values in the reference population. GFR decreased with increasing age, where 11.4% and 5.6% of AF patients aged ≥ 75 years had eGFR < 30 ml/min/1.73 m² according to the LM and MDRD equations, respectively.

Conclusions

Severe renal impairment is common among AF patients on anticoagulant treatment with warfarin, especially at higher ages. Monitoring of renal function should be implemented in clinical practice for AF patients treated with new anticoagulants eliminated by the kidneys.     

卡托普利对大鼠肝纤维化治疗作用的实验研究

目的 探讨卡托普利对大鼠肝纤维化的治疗作用及其机制.方法 采用四氯化碳(CCl4)制造大鼠肝纤维化模型,设正常组、模型组、卡托普利低剂量组和卡托普利高剂量组,采用放射免疫法测定血液和肝匀浆中肾素活性、血管紧张素和醛固酮;采用紫外分光光度法测定血管紧张素转换酶活性;图像分析法判定肝纤维化程度.结果 卡托普利能降低肝内肾素-血管紧张素-醛固酮系统(RAAS)活性(P＜0.01),减轻肝纤维化(P＜0.01),两剂量之间差异无显著性.结论 卡托普利具有抗肝纤维化作用;其机制可能是抑制肝内RMS激活.     

Epoxyeicosatrienoic acids--novel mechanism and pharmacological therapy of chronic renocardiac syndrome

Cardiorenal syndromes were defined and classified recently, but the mechanism of chronic renocardiac syndrome remains disputed. Theories about chronic renocardiac syndrome cannot offer a convincing explanation for it. As a result, the current therapies of chronic renocardiac syndrome do not contribute to a satisfied prognosis. Epoxyeicosatrienoic acids, the products of arachidonic acid metabolized by cytochrome P450 enzymes, play an important role in the maintenance of renal hemodynamics, and regulation of renal, cardiac, and vascular function with antihypertensive and anti-inflammatory properties. It is well documented that down-regulation of epoxyeicosatrienoic acids might be involved in alterations in various pathophysiological states, including hypertension, uremia and hepatorenal syndrome. Likewise, epoxyeicosatrienoic acids were reduced in heart failure and renal dysfunction. This leads to the proposed hypothesis that epoxyeicosatrienoic acids down-regulation may be the novel mechanism of chronic renocardiac syndrome. These findings suggest that manipulation of epoxyeicosatrienoic acid levels could be a novel pharmacological therapy strategy for chronic renocardiac syndrome.