高血压与炎症的研究进展

高血压病的发生机制是一个复杂的病理过程。其中,全身动脉血管炎症反应参与高血压的病理生理过程,它是多种炎症细胞、递质、细胞因子共同作用的结果。现综述炎性细胞、炎性细胞因子在高血压发生发展过程中的作用,并介绍高血压的抗炎治疗进展。     

全身免疫炎症指数与高血压病相关性的研究进展

高血压病是世界范围内最常见的慢性疾病之一,目前认为高血压与炎症和免疫密切相关。全身免疫炎症指数是一种新型炎症标志物,已经被用来研究与高血压的相关性。阐述全身免疫炎症指数与高血压患病率的关系、促进原发性高血压的机制,并对全身免疫炎症指数与原发性高血压病人性别、血压变异性、靶器官损害及预后等方面进行综述。     

Notch信号通路与高血压的关系

原发性高血压(essential hypertension,EH)是最常见的心血管疾病之一,更是诱发脑中风、冠心病、心力衰竭等常见重大疾病的主要危险因素。目前认为高血压是多基因、多诱因相互作用的结果,特别是遗传因素、膳食、神经内分泌、炎症等多种机制在高血压的发生发展中起着十分重要的作用。炎症作为一种高血压发病机制近来备受关注。单纯高血压病人血浆中TNF-     

TLR4/MyD88通路与高血压及中药干预此通路的研究进展

探讨信号通路TLR4/MyD88在高血压病中的作用,及以信号通路中相关蛋白及相应RNA为靶点进行高血压病的中药抗感染治疗。介绍信号通路系统组成及激活途径,信号通路与炎症、炎症与高血压的关系,以信号通路相关蛋白及相应RNA为靶点,中药进行高血压的抗感染治疗。信号通路在高血压炎症的发生机制中可能发挥着一定的作用,这为高血压治疗提供了新的治疗靶点。     

高血压病与炎症反应相关性的研究进展

越来越多的证据表明,炎症反应与原发性高血压病之间存在相关性。炎症因子会增加高血压病的患病率,并影响高血压病患者的诊断、治疗和预后。因此,采用一种新的治疗途径去干扰炎症反应和氧化应激可能会改善高血压患者的预后,延缓和减少血管并发症的发生。     

炎症与高血压应对策略

炎症在心血管疾病的发生、发展和并发症的出现中表现出了越来越重要的作用。冠心病与炎症的关系已得到公认，高血压与炎症的关系也愈加受到重视。研究发现高血压病病人C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）等炎症因子明显升高，且呈高度相关，证实高血压是一个低度的炎症状态性疾病。炎症在高血压血管重构、心肌重构和肾脏间质重构中也发挥着负面效应。近年来的临床研究和流行病学调查发现，血管紧张素转换酶抑制剂（ACEI）和血管紧张素Ⅱ受体拮抗剂（ARB）等类药物有降血压外的抗炎效应，非药物干预方法如：富含不饱和脂肪酸饮食、有氧运动等也能改善高血压病病人的血管炎症状态，提高血管内皮功能等作用。     

辛伐他汀对冠心病患者C反应蛋白的影响

血管内皮损伤所致的内皮功能障碍被认为是高血压病可能的发病机制之一，内皮损伤所引发的炎症反应同高血压的发生、发展密切相关。C反应蛋白是机体炎症反应一种敏感但非特异性标志物。本文通过研究冠心病（CHD）患者应用他汀类药物后C反应蛋白的变化，评估其对冠心病发生发展和预后的价值。     

干预炎症反应改善糖尿病心肌病的作用研究进展

糖尿病心肌病是糖尿病主要的心血管疾病并发症之一,是独立于冠心病、高血压病、重大心脏瓣膜疾病的以早期舒张功能损害并伴有心肌肥厚、心肌纤维化和心肌细胞凋亡的疾病,其发病虽与高血糖明确相关,但近些年研究发现,糖尿病早期心脏即出现慢性、低度的炎症反应,后者参与了糖尿病心肌病的发生和发展。本文就炎症反应在糖尿病心肌病发生、发展过程中的作用以及相关的炎症反应干预研究进展进行阐述。     

高敏C反应蛋白与高血压病心房颤动的关系

目的探讨高敏C反应蛋白（hs-CRP）作为系统炎症因子在高血压病心房颤动（房颤）发生和发展中的作用。方法将137例高血压病患者分为高血压无房颤组41例、阵发性房颤组43例和持续性房颤组53例,测定并比较各组hs-CRP水平、左心房内径（LA）。结果血清hs-CRP水平阵发性房颤组比高血压无房颤组明显增高（P〈0.01）,持续性房颤组高于阵发性房颤组（P〈0.01）。LA与hs-CRP水平呈正相关（r=0.56,P〈0.05）。结论hs-CRP在高血压病房颤的发生和维持中起一定作用。     

原发性高血压与A型性格相关性临床分析

高血压病（原发性高血压）是常见的心血管疾病^[1]，原发性高血压的发病率在我国呈逐年增加的趋势，原发性高血压在21世纪心血管病中占第一位，病因复杂，既往研究认为生物因素在高血压病的发生，发展中起主要作用。近年来随着生物医学模式转变，人们开始重视心理因素对疾病发生，发展的作用。高血压病是一种被公认的心身疾病。Buell提出A型行为类型与高血压病的发病有关，本文采用A型行为问卷，焦虑抑郁自评量表对高血压病人和正常人对照进行测试，以分析高血压病与A型性格的相关性。     

Pulmonary arterial hypertension associated to connective tissue diseases

Pulmonary arterial hypertension is a well-known complication of connective tissue diseases such as systemic sclerosis, systemic lupus erythematosus, mixed connective tissue diseases, and to a lesser extent, rheumatoid arthritis, dermatopolymyositis and primary Sj?gren's syndrome. In these patients, pulmonary hypertension may occur in association with left heart disease, interstitial fibrosis or as a result of a isolated pulmonary arteriopathy. The incidence of pulmonary arterial hypertension in the limited form of systemic sclerosis is about 10%. The pathophysiologic mechanisms leading to pulmonary arterial hypertension remain unknown. Symptoms and clinical presentation are very similar to idiopathic pulmonary arterial hypertension but mortality was confirmed to be higher. Echocardiography is the reference investigation for the detection of pulmonary arterial hypertension but the results should be confirmed by right heart catheterization. Treatment appears more complex as compared to idiopathic pulmonary arterial hypertension. Intravenous epoprostenol therapy has been shown to be effective in a special trail. Also, the endothelin receptor antagonists bosentan and sitaxentan, the phosphodyesterase-type-5 sildenafil and subcutaneous treprostinil have shown favourable results.     

Fifty years of Framingham Study contributions to understanding hypertension

The Framingham Study established hypertension as a major cardiovascular risk factor and quantified its atherogenic cardiovascular disease potential. An historical perspective is presented on the epidemiological insights about hypertension derived from 50 years of Framingham Study research into the prevalence, incidence, determinants and hazards of hypertension. Existing misconceptions about the presence of critical levels of blood pressure, the impact of the systolic and diastolic components of blood pressure, the hazard 'mild' hypertension, the impact in advanced age and the hazard of left ventricular hypertrophy. The importance of isolated systolic hypertension and the pulse pressure were demonstrated. It has been demonstrated that hypertension seldom occurs in isolation of other atherogenic risk factors, with which it tends to cluster. This clustering with other metabolically linked risk factors has been shown to reflect insulin resistance promoted by weight gain and abdominal obesity. Obesity was shown to be one of the major determinants of hypertension in the general population. Left ventricular hypertrophy was shown to be an ominous harbinger of cardiovascular disease rather than an incidental compensatory phenomenon. Multivariate risk profiles for coronary disease, stroke, peripheral artery disease and heart failure have been devised to facilitate incorporation of elevated blood pressure in a global, multivariate cardiovascular risk assessment.     

Endothelium-dependent vasodilation in hypertension: a review

Using both in vitro and in vivo techniques, it has repeatedly been shown that endothelium-dependent vasodilation (EDV) is impaired in different forms of experimental hypertension (SHR, Dahl salt-sensitive rat, DOCA-salt rat and renovascular hypertension). EDV has also been found to be impaired in primary, as well as in secondary forms of human hypertension. Although impaired EDV is a general finding in hypertension, the pathophysiological mechanisms might differ between different forms of hypertension and between different types of vessels and vascular beds. Impaired activity of nitric oxide synthase, increased release of endothelin-1, increased production of a prostanoid-derived contracting factor, decreased generation of endothelium-derived hyperpolarizing factor/s and impairment caused by superoxide ions have all been shown to contribute to the impairment of EDV during different conditions. While most antihypertensive treatments improve EDV in experimental hypertension, no uniform picture has been seen in human hypertension, possibly because different antihypertensive drugs have different direct actions on EDV. This review shows that while impaired EDV has been found to be a general feature of hypertension, the mechanisms involved and the therapeutic opportunities have still to be established.     

Various indices of the kallikrein-kinin and clotting systems of the blood of patients with acute myocardial infarcts with and without essential hypertension

The kinin and coagulation functions were examined in 78 myocardial infarction patients in relation to the presence of essential hypertension. The kallikrein-kinin activation and blood hypercoagulation were shown to be more pronounced in cases of associated essential hypertension.     

p38 MAP kinase isoform activity and cell cycle regulators in the proliferative response of pulmonary and systemic artery fibroblasts to acute hypoxia

Many cardiopulmonary diseases are associated with pulmonary hypertension which adds significant co-morbidity. Pulmonary hypertension is due partly to vasoconstriction but sustained by pulmonary vascular remodelling. If pathological endpoints are to be reversed in patients with pulmonary hypertension, the processes by which vascular remodelling occur need to be determined. Hypoxia provides a good model of pulmonary hypertension. We have previously shown that chronic hypoxia results in increased proliferation of pulmonary artery fibroblasts and stimulation of the mitogen-activated protein kinase (MAPK) family of signalling enzymes. Under the same conditions systemic artery fibroblasts were unaffected. This differential response of pulmonary fibroblasts to hypoxia represents a model to investigate the processes of pulmonary artery remodelling. The current study showed that acute hypoxia was capable of causing enhanced proliferation in pulmonary but not systemic artery fibroblasts and was linked to increased activation of p38 MAP kinase. Second, we have now shown that it is alpha and gamma isoforms of p38 MAP kinase, which are responsible. Third we have shown a link between stimulation of p38 MAP kinase and HIF-1 proportional, variant induction. An increased understanding of the effects of hypoxia on remodelling and proliferation represents a critical step in identifying targets for the treatment of pulmonary hypertension.     

Detection and Treatment of Resistant Hypertension

The evaluation of patients with resistant hypertension should be directed toward confirming true treatment resistance, identifying the causes contributing to treatment resistance (including secondary causes of hypertension), and documenting target-organ damage. Treatment of resistant hypertension is aimed at reversing lifestyle factors contributing to treatment resistance, accurately diagnosing and appropriately treating secondary causes of hypertension, and effectively using multidrug regimens. Lifestyle changes, pharmacologic therapies, and nonpharmacologic therapies have all shown benefits in patients with resistant hypertension, but much additional knowledge is needed to better identify and treat these patients.     

Systemic hypertension: the roles of salt, vascular Na+/K+ ATPase and the endogenous glycosides, ouabain and marinobufagenin

Essential hypertension has been shown to be significantly associated with an increased risk for cardiovascular disease and is not well controlled in many patients. In a large portion of people with essential hypertension, sodium intake has been shown to play a significant role in the production of their hypertension. The mechanism through which increased sodium intake manifests hypertension is unresolved and likely multifactorial. Endogenous cardiac glycosides such as endogenous ouabain (EO) and marinobufagenin have been proposed to play a role in salt-sensitive essential hypertension through their inhibition of Na/K ATPase (NKA). The normal function of the NKA pump is to extrude Na from the intracellular environment and import K. Blocking the NKA disrupts its normal maintenance function. EO is proposed to produce alteration in smooth muscle cell contractility by inhibiting the α2-isoform of NKA, altering Na in a microdomain of the cell. In this region of the plasma membrane the α2-isoform of the NKA colocalizes with another transmembrane protein, the Na/Ca exchanger (NCX). The normal function of NCX is to extrude Ca and import Na. Inhibition of NKA produces an increase in Na within the microdomain, which in turn alters the function of the NCX so that less Ca is extruded, leading to increased intracellular Ca and increased vascular contraction. EO has been shown to be synthesized and secreted by the adrenal cortex in response to chronically elevated sodium intake. The levels of EO have been shown to be significantly elevated in 40% of all untreated hypertensive patients. Marinobufagenin, another cardiac glycoside, has also been implicated as a possible cause of essential hypertension through its preferential inhibition of the α1-isoform of NKA. Antagonism of the endogenous inhibitors of NKA is currently a target of clinical research for the development of innovative antihypertensive treatments.     

Protein kinase A and C activity of erythrocytes in patients with essential hypertension

Activities of protein kinases A and C in erythrocyte cytoplasmic fraction purified by CM-Sephadex and DEAE-cellulose have been measured. Protein kinase C activity is shown to be 1.6-1.8-fold higher, as compared to controls, in essential hypertension, but remain unchanged in renal hypertension. Protein kinase A activity is slightly elevated in patients with essential hypertension, but the difference is not significant. It is suggested that the increase of protein kinase C activity, and perhaps some other activities as well, in essential hypertension may be a result of altered expression of protooncogenes with protein kinase activities.     

Should we routinely measure portal pressure in patients with cirrhosis, using hepatic venous pressure gradient (HVPG) as guidance for prophylaxis and treatment of bleeding and re-bleeding? Yes!

Portal hypertension is key to the natural history of cirrhosis. The standard way to assess portal hypertension is the hepatic venous pressure gradient (HVPG). HVPG has been convincingly shown to be a strong predictor of variceal bleeding and survival. In addition, it has been shown to predict other portal hypertension-related clinical events, to include fluid retention and hepatic encephalopathy. Finally, HVPG is the only suitable tool to assess the response of portal hypertension to medical treatment. Thus, although not necessarily easy to measure, HVPG provides the clinician with information which is prognostically crucial and otherwise unobtainable.     

Prehypertension: A possible target for antihypertensive medication

Vascular changes associated with elevated blood pressure may precede the clinical diagnosis of hypertension. Even after the diagnosis is made, associated coronary heart disease and renal disease continue to progress, despite adequate blood pressure control. Early treatment of blood pressure may reduce the incidence of clinical hypertension and reduce the long-term consequences of hypertension. Animal studies have shown that early blood pressure lowering, through blockade of the renin-angiotensin system, prevents long-term hypertension. Prevention is an important goal in the treatment of hypertension. Our best attempts to prevent hypertension use nonpharmacologic methods of diet and exercise. These methods are fraught with difficulties of implementation and compliance that limit their success. Finding novel approaches to prevent hypertension may have a major impact on the incidence of hypertension. We are investigating the effect of 2 years of treatment with an angiotensin receptor blocker (candesartan cilexitil) compared with placebo, followed by 2 years of follow-up, on the incidence of hypertension in patients with high-normal blood pressure. Incidence of hypertension after discontinuation of active treatment will be compared with the incidence in the placebo group. There will be 1000 patients enrolled in the study, which will be completed in 2004.