In hypertension,the kidney rules

The renin-angiotensin system (RAS) is a critical regulator of blood pressure and fluid homeostasis. Components of the RAS, including renin, angiotensin-converting enzyme (ACE), and angiotensin type 1 (AT1) receptors, are expressed throughout the body in tissues that may impact blood pressure control. Blocking actions of individual components of the RAS lowers blood pressure. Although it has been suggested that control of sodium excretion by the kidney is the dominant mechanism for blood pressure regulation by the RAS, pharmacologic antagonists or conventional gene targeting experiments globally interrupt the RAS and cannot discriminate its actions in the kidney from other tissue compartments. Recent experiments using kidney cross-transplantation and genetically engineered mice have confirmed a major role for angiotensin II acting via AT1 receptors in the kidney in hypertension. These actions of renal AT1 receptors are required for the development of angiotensin II-dependent hypertension and cardiac hypertrophy. These findings, with previous experiments, clearly establish the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications.     

The heart,kidney, and brain as target organs in hypertension

The heart, kidney, brain, and arterial blood vessels are prime targets of hypertensive damage. Uncontrolled hypertension accelerates the damage to these organs and results in eventual organ failure and cardiovascular death and disability. Current guidelines for the appropriate treatment and control of hypertension requires an assessment of the presence of target organ damage. When present, evidence of target organ damage determines the urgency and intensity of drug treatment and may also dictate the choice of initial antihypertensive drug class. Thus, evaluation of persons with suspected or established hypertension must include a meticulous search for evidence of target organ damage. Fortunately, treatment with all antihypertensive medications that results in significant BP reductions also reduces fatal and nonfatal hypertensive complications and significantly slows down the progression to organ failure. Because of the important role that adverse activation of the renin-angiotensin-aldosterone system plays in target organ damage, drugs that antagonize this system have provided consistent and compelling proof of organ protection in both primary and secondary prevention of adverse outcomes. The challenge now is to use these and all other antihypertensive agents effectively to control BP to target levels in patients with hypertension. Continued emphasis on the adoption of lifestyle changes for prevention of hypertension in the first place or as adjunctive therapy in hypertensive patients is essential.     

The heart,kidney, and brain as target organs in hypertension

The heart, kidney, brain, and arterial blood vessels are prime targets of hypertensive damage. Uncontrolled hypertension accelerates the damage to these organs and results in eventual organ failure and cardiovascular death and disability. Current guidelines for the appropriate treatment and control of hypertension requires an assessment of the presence of target organ damage. When present, evidence of target organ damage determines the urgency and intensity of drug treatment and may also dictate the choice of initial antihypertensive drug class. Thus, evaluation of persons with suspected or established hypertension must include a meticulous search for evidence of target organ damage. Fortunately, treatment with all antihypertensive medications that results in significant BP reductions also reduces fatal and nonfatal hypertensive complications and significantly slows down the progression to organ failure. Because of the important role that adverse activation of the renin-angiotensin-aldosterone system plays in target organ damage, drugs that antagonize this system have provided consistent and compelling proof of organ protection in both primary and secondary prevention of adverse outcomes. The challenge now is to use these and all other antihypertensive agents effectively to control BP to target levels in patients with hypertension. Continued emphasis on the adoption of lifestyle changes for prevention of hypertension in the first place or as adjunctive therapy in hypertensive patients is essential.     

Endothelin, the kidney, and hypertension

The kidneys play a central role in the long-term regulation of blood pressure and in the pathogenesis of hypertension. A common defect that has been found in all forms of hypertension examined to date is a hypertensive shift in the pressure-natriuresis relationship. A major objective of this brief review is to highlight some of the recent advances in our understanding of the mechanisms whereby the renal endothelin system, via endothelin type A- and endothelin type B-receptor activation, modulates renal pressure-natriuresis and blood pressure regulation under normal physiologic conditions and in certain forms of hypertension.     

Cyclooxygenases, the kidney, and hypertension

Selective cyclooxygenase (COX)-2 inhibitors that are in widespread clinical use were developed to avoid side effects of conventional NSAIDs, including gastrointestinal and renal toxicity. However, COX-2 is constitutively expressed in the kidney and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in maintenance of renal blood flow, mediation of renin release, and regulation of sodium excretion. COX-2 inhibition may transiently decrease urine sodium excretion in some subjects and induce mild to moderate elevation of blood pressure. Furthermore, in conditions of relative intravascular volume depletion and/or renal hypoperfusion, interference with COX-2 activity can have deleterious effects on maintenance of renal blood flow and glomerular filtration rate. In addition to physiological regulation of COX-2 expression in the kidney, increased renal cortical COX-2 expression is seen in experimental models associated with altered renal hemodynamics and progressive renal injury (decreased renal mass, poorly controlled diabetes), and long-term treatment with selective COX-2 inhibitors ameliorates functional and structural renal damage in these conditions.     

保护心脑肾是高血压病治疗的重要目标

高血压不仅会造成靶器官的损害,还是心血管疾病患者致死致残的重要原因。高血压治疗的现代理念是保护患者脑、心、肾和血管等靶器官不受损害。采取严格控制血压、个体化治疗、优化联合用药及综合干预是保护心脑肾不受损害的有效对策。     

Obesity, hypertension, and the heart

Hypertension occurs more commonly in obese than in lean persons at virtually every age. A variety of endocrine, genetic, and metabolic mechanisms have been linked to the development of obesity hypertension. These include insulin resistance and hyperinsulinemia, increased serum aldosterone levels, salt sensitivity and expanded plasma volume in the presence of increased peripheral vascular resistance, a genetic predisposition, and possibly increased leptin levels. Pressure and volume overload are present in obese hypertensives. This leads to a mixed eccentric-concentric form of left ventricular hypertrophy and increases the predisposition to congestive heart failure. Weight loss, even in modest decrements, is effective in reducing obesity-hypertension, possibly by ameliorating several of the proposed pathophysiologic mechanisms. There are currently no specific recommendations concerning pharmacotherapy of obesity-hypertension because each drug group has pros and cons.     

Obesity, hypertension, and the heart

Controversy exists regarding the amount of risk caused by obesity, but there is general consensus that it is associated with many serious disorders, mostly cardiovascular and neoplastic. Obesity is clearly associated with hypertension, ventricular remodeling with subsequent congestive heart failure, sleep-disordered breathing, and sudden death. The physiologic alterations associated with establishing and perpetuating the obese state are complex but are becoming clear. In discussing the cardiovascular consequences of obesity, the implications and mechanism of the associated hypertension need to be understood. There is growing recognition that adipose tissue is a very active in the neurohormonal axis and is not simply a passive storage depot. Among other things, adipocyte-related hormonal activity and resistance to feedback mechanisms are associated with increased plasma volume and increased sympathetic tone.     

Systemic hypertension, diabetes mellitus and the kidney

Diabetic nephropathy is manifested by albuminuria, hypertension and progressive loss of renal function. Only one-third of patients with insulin-dependent diabetes mellitus of juvenile onset develop nephropathy and the risk of nephropathy does not increase with increasing duration of diabetes. Hypertension occurs almost exclusively in patients with nephropathy. Therefore, there is a subset of patients at risk for both nephropathy and hypertension. It is important to identify the patients destined to develop nephropathy, to define the pathophysiology responsible for the nephropathy in this subset of patients and to develop programs to interrupt the pathophysiology early in its course and hopefully prevent the progression to end-stage renal failure. Potential markers to identify patients who will develop nephropathy include a family history of hypertension, increased glomerular filtration rate and renal mass and presence of significant microalbuminuria. Studies are needed to evaluate various classes of drugs for their efficacy in altering the pathophysiologic hemodynamic changes leading to nephropathy.     

Diabetes mellitus, hypertension and kidney

The correlations co-exist among diabetes mellitus, hypertension and the kidney. Renal injury will develop in 35% type 1 and type 2 diabetes mellitus patients. Diabetic nephropathy is the key factor for the occurence of hypertension in type 1 diabetes mellitus. In case of type 2 diabetes mellitus with prevalent essencial hypertension the diabetic nephropathy is supporting factor for the development of hypertension. Untreated or inadequately treated hypertension accelerates the progression of diabetic renal impairment. The presence of diabetes mellitus as well as hypertension or proteinuria is significant cardiovascular risk factor. The goal of treatment with angiotensin converting enzyme inhibitors or AT1 receptor of angiotensin II blockers is both slowing-down of renal injury progression and reduction in risk of cardiovascular complications.     

老年单纯收缩期高血压对心脑肾损害临床观察

目的探讨老年单纯收缩压升高对心、脑、肾等器官损害情况。方法收集本院１９８７～１９９６年心内科门诊老年单纯收缩期高血压患者１９４例进行回顾性分析。结果发生心力衰竭４９例（２５．２６％）；每搏出量（ＳＶ）＜７０ｍｌ／次９２例（４７．４２％），心排出量（ＣＯ）＜５．０Ｌ／ｍｉｎ８０例（４１．２３％），排血指数（ＳＶＩ）＜４８ｍｌ次－１／ｍ２９８例（５０．５２％），心脏指数（ＣＩ）＜３．２Ｌｍｉｎ－１／ｍ２６８例（３５．０５％），左室射血分数（ＬＶＥＦ）＜０．４０者４６例（２３．７１％）。ＳＴ－Ｔ呈缺血性改变７５例（３８．６６％）；ＰｔｆＶ１＜－０．０４ｍｍｓ７７例（３９．６９％）；心律失常１０６例（５１．５５％）；脑血管意外３２例（１６．４９％），其中脑梗塞２２例（１１．３４％），脑出血１０例（５．１５％）；肾脏受损５１例（２６．２９％）；胰腺受损１３例（６．７０％）。结论老年单纯收缩期高血压对心、脑、肾等器官的损害是很多见的，其预后不容乐观。     

Fatty kidney, hypertension, and chronic kidney disease: the Framingham Heart Study

Ectopic fat depots may mediate local and systemic disease. Animal models of diet-induced obesity demonstrate increased fat accumulation in the renal sinus. The association of renal sinus fat with hypertension, chronic kidney disease, and other metabolic disorders has not been studied in a large, community-based sample. Participants from the Framingham Heart Study (n=2923; mean age: 54 years; 51% women) underwent quantification of renal sinus fat area using computed tomography. High renal sinus fat ("fatty kidney") was defined using sex-specific 90th percentiles in a healthy referent subsample. Multivariable linear and logistic regression was used to model metabolic risk factors as a function of fatty kidney and log-transformed renal sinus fat. Multivariable models were adjusted for age, sex, and outcome-specific covariates and then additionally adjusted for body mass index or abdominal visceral adipose tissue. The prevalence of fatty kidney was 30.1% (n=879). Individuals with fatty kidney had a higher odds ratio (OR) of hypertension (OR: 2.12; P<0.0001), which persisted after adjustment for body mass index (OR: 1.49; P<0.0001) or visceral adipose tissue (OR: 1.24; P=0.049). Fatty kidney was also associated with an increased OR for chronic kidney disease (OR: 2.30; P=0.005), even after additionally adjusting for body mass index (OR: 1.86; P=0.04) or visceral adipose tissue (OR: 1.86; P=0.05). We observed no association between fatty kidney and diabetes mellitus after adjusting for visceral adipose tissue. In conclusion, fatty kidney is a common condition that is associated with an increased risk of hypertension and chronic kidney disease. Renal sinus fat may play a role in blood pressure regulation and chronic kidney disease.