Interactive effects of serum ferritin and high sensitivity C-reactive protein on diabetes in hypertensive patients

BackgroundHypertensive patients, often characterized by chronic inflammation, are susceptible to diabetes. Evidence suggests that the positive association between serum ferritin (SF) and diabetes was affected by high-sensitivity C-reactive protein (hs-CRP), an inflammation marker. We investigate whether there was an interaction between SF and hs-CRP on diabetes in hypertensive patients.MethodsWe analysed data of 1,735 hypertensive people in this cross-sectional study. Diabetes was diagnosed when fasting blood glucose ≥ 7.0 mmol/L and/or a previous clinical diagnosis of diabetes. Logistic regression models were used to estimate the association of the SF and hs-CRP with diabetes. Multiplicative interaction was evaluated by incorporating a cross-product term for SF and hs-CRP to the logistic regression model. Additive interaction was assessed by calculating the relative excess risk of interaction (RERI) and attributed proportion due to interaction (AP).ResultsIn the adjusted analysis, SF (highest vs lowest tertile: odds ratio [OR], 1.61; 95 % confidence interval [CI], 1.20−2.16) was positively associated with diabetes. There was no multiplicative interaction between SF and hs-CRP, but evidence of additive interaction in regard to diabetes (RERI: 0.86; 95 % CI: 0.06−1.67). Compared to the patients with low SF (lower two thirds) and low hs-CRP (≤ 2 mg/L), those with high SF (upper one third) and high hs-CRP (> 2 mg/L) had increased OR for diabetes (adjusted OR: 2.33 [1.65−3.30]), with 37.0 % of the effects attributed to the additive interaction (AP: 0.37; 95 % CI: 0.09−0.65).ConclusionsWithin a cross-sectional study consisting of hypertensive patients, co-exposure to high SF and high hs-CRP was synergistically associated with diabetes. Dietary intervention or pharmacological treatment to lowering SF concentration may help to reduce diabetes morbidity in hypertensive patient with chronic inflammation.     

Stroke: development, prevention and treatment with peptidase inhibitors

Stroke is the leading cause of long-term disability in the United States and affects more people than any other neurologic disorder. Hypertension is a major risk factor associated with stroke. Several anti-hypertensive agents have been used to treat chronic hypertension to reduce the morbidity and mortality of stroke. Previous experimental studies have shown reduced stroke mortality with angiotensin-converting enzyme (ACE) inhibitors. This review discusses the development of stroke and potential use of ACE inhibitors in prevention and treatment of this disease. Furthermore, this review focuses on current investigations aimed at cellular mechanisms involved in stroke-induced microvascular alterations.     

赖诺普利联合坎地沙坦治疗心力衰竭合并原发性高血压

目的：观察和评价赖诺普利联合坎地沙坦治疗心力衰竭（HF）合并原发性高血压（EH）的疗效。方法：将我院收治的EH合并HF患者69例,在给予个体化治疗的基础上随机分为：A组赖诺普利治疗组,B组坎地沙坦治疗组,C组赖诺普利和坎地沙坦联合治疗组,三组疗程均为8周。观察治疗前后的血压、心功能分级、BNP水平、心脏彩色多普勒及肝肾功检查。结果：与对照组比较,联合组的总有效率明显增高,差异有统计学意义;治疗前后所有患者肝肾功能等生化指标未见明显变化。结论：赖诺普利与坎地沙坦联合治疗心力衰竭合并原发性高血压的疗效明显优于单用赖诺普利或坎地沙坦的疗效,且安全性好,值得广泛推广和应用。     

微血管自律运动在高血压发生发展中的变化和意义

微循环的异常,包括微血管的稀疏和（或）微血管结构的改变,可能参与了高血压的发生发展,是造成终末器官缺血和功能障碍直至衰竭的主要原因之一。根据文献报道,微血管自律运动调控血流动力学的同时还参与信息传递并适时作出反应,改善组织灌注不足、缺血、缺氧,缓解外周压力。已有研究发现,高血压发生发展过程中,微血管自律运动频率和振幅呈现复杂的变化,可能与内皮细胞功能不足、细胞间缝隙连接减少、平滑肌细胞钙离子内流增多及钙池功能异常引起膜电位改变等有关,本文将从微循环的角度阐述高血压状态下微血管自律运动的变化并对其机制做一简要概述。     

原发性高血压合并冠心病患者血清CRP的变化

目的:探讨原发性高血压合并不同类型冠心病患者血清C-反应蛋白(CRP)的变化及其意义。方法:用全自动生化分析仪检测71例原发性高血压患者和28例健康对照组人群的血清CRP水平,所有研究对象均行选择性冠状动脉造影检查。将原发性高血压组病人根据冠脉造影检查分为单纯原发性高血压组(EH),原发性高血压合并稳定性心绞痛组(EH+SAP)、原发性高血压合并不稳定心绞痛组(EH+UAP)、原发性高血压合并心肌梗死组(EH+MI),比较各组患者血清CRP水平的差异。结果:①与对照组比较,EH组及EH合并CAD各组患者血清CRP均显著升高(P0.05);②与EH组比较,EH+UAP和EH+MI组血清CRP水平均显著升高(P0.01);③与EH+SAP组比较,EH+AMI组和EH+UAP组血清CRP水平均显著升高(P0.01)。结论:冠心病合并原发性高血压患者血CRP水平与冠状动脉病变程度与斑块稳定程度存在正相关性。     

Distinct binding mode of I-AngII to AT1 receptor without the Cys-Cys disulfide bridge

Previous studies have shown that different parts of the septal area may have opposite roles in the control of water intake and cardiovascular responses. In the present study we investigated the effects of electrolytic lesions of the intermediate nucleus of the lateral septal area (LSI) on cardiovascular and dipsogenic responses to intracerebroventricular (icv) angiotensin II (ANG II) and water intake induced by other different stimuli. Male Holtzman rats (280–320 g of body weight, n = 6–16/group) with sham or electrolytic lesions of the LSI and a stainless steel cannula implanted into the lateral ventricle (LV) were used. The LSI lesions did not affect body weight or daily water intake. However, LSI lesions reduced water intake and pressor responses induced by icv ANG II (4.10^− 2 nmol). The LSI lesions also slightly reduced water intake induced by 24 h of water deprivation or isoproterenol (30 μg/kg) subcutaneously, but did not affect water intake induced by intragastric 2 ml of 2 M NaCl load. The results suggest that LSI is part of the forebrain circuitry activated by ANG II to produce pressor and dipsogenic responses. However, the same nucleus is not involved in the dipsogenic responses to central osmoreceptor activation.     

Altered regulation of renal sodium transporters and natriuretic peptide system in DOCA–salt hypertensive rats

Although deoxycorticosterone acetate (DOCA)–salt hypertension is a volume dependent model of hypertension, it shows polyuria and natriuresis. It is expected that dysregulation of aquaporin water channels (AQPs) and sodium transporters associated with natriuretic peptide (NP) system may play an escape role in sodium retaining state. One week after left unilateral nephrectomy, rats were subcutaneously implanted with silastic DOCA (200 mg/kg) strips. Physiologic saline was supplied as a drinking water to all animals. 4 weeks after operation, the protein expression of AQPs, sodium transporters, and endopeptidase (NEP) was determined in the kidneys by semiquantitative immunoblotting and immunohistochemistry. The mRNA expression of NP system was determined by real-time polymerase chain reaction. The amount of urinary ANP excretion was measured by radioimmunoassay. In DOCA–salt rats, urine osmolality was decreased while urinary excretion of sodium was increased. The expression of AQP1-3 as well as that of α-1 subunit of Na,K–ATPase, NHE3, NKCC2 and NCC was decreased in the kidney. The mRNA expression of ANP, brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP) was increased in the kidney. The expression of NEP was decreased, and urinary ANP excretion was increased. Downregulation of AQPs and sodium transporters may contribute to mineralocorticoid escape in DOCA–salt hypertension. Increased expression of natriuretic peptides associated with downregulation of NEP may play a role in natriuresis.     

PPARα agonist fenofibrate protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress and MAPK activity

Oxidative stress has been shown to play an important role in the development of hypertensive renal injury. Peroxisome proliferator-activated receptors α (PPARα) has antioxidant effect. In this study, we demonstrated that fenofibrate significantly reduced proteinuria, inflammatory cell recruitment and extracellular matrix (ECM) proteins deposition in the kidney of SHRs without apparent effect on blood pressure. To investigate the mechanisms involved, we found that fenofibrate treatment markedly reduced oxidative stress accompanied by reduced activity of renal NAD(P)H oxidase, increased activity of Cu/Zn SOD, and decreased phosphorylation of p38MAPK and JNK in the kidney of SHRs.Taken together, fenofibrate treatment can protect against hypertensive renal injury without affecting blood pressure by inhibiting inflammation and fibrosis via suppression of oxidative stress and MAPK activity.     

Improvement of diabetes, obesity and hypertension in type 2 diabetic KKAy mice by bis(allixinato)oxovanadium(IV) complex

Previously, we found that bis(allixinato)oxovanadium(IV) (VO(alx)(2)) exhibits a potent hypoglycemic activity in type 1-like diabetic mice. Since the enhancement of insulin sensitivity is involved in one of the mechanisms by which vanadium exerts its anti-diabetic effects, VO(alx)(2) was further tested in type 2 diabetes with low insulin sensitivity. The effect of oral administration of VO(alx)(2) was examined in obesity-linked type 2 diabetic KKA(y) mice. Treatment of VO(alx)(2) for 4 weeks normalized hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia and hypertension in KKA(y) mice; however, it had no effect on hypoadiponectinemia. VO(alx)(2) also improved hyperleptinemia, following attenuation of obesity in KKA(y) mice. This is the first example in which a vanadium compound improved leptin resistance in type 2 diabetes by oral administration. On the basis of these results, VO(alx)(2) is proposed to enhance not only insulin sensitivity but also leptin sensitivity, which in turn improves diabetes, obesity and hypertension in an obesity-linked type 2 diabetic animal.