Renal Autotransplantation for Uncontrolled Hypertension in Nonatherosclerotic Renal Artery Stenosis-2 Case Reports and a Brief Review of the Literature.

Fibromuscular dysplasia is the most common cause of renovascular hypertension in young adults under 40 years old. It is potentially amenable to renal artery angioplasty, which frequently normalizes blood pressure. However, limited options exist if angioplasty is not technically possible, or restenosis occurs. Here, we describe 2 patients who presented with hypertension secondary to renal artery stenosis. In the first case, a young adult with hypertension secondary to renal artery stenosis (fibromuscular dysplasia), developed restenosis 11 weeks after an initially successful renal artery angioplasty. In the second case, a patient with neurofibromatosis type 1 was diagnosed with hypertension secondary to renal artery stenosis. Angioplasty was not possible due to multiple branch occlusions. Both individuals went on to have successful renal autotransplantations, which ultimately cured their hypertension. In this article, we review the background, indications, and blood pressure outcomes in relation to renal autotransplantation in nonatherosclerotic renal artery stenosis.

Endovascular Versus Medical Management of Atherosclerotic Renovascular Disease: Update and Emerging Concepts.

Atherosclerotic renovascular disease is the most frequent cause of renovascular hypertension and its prevalence increases with age and in specific subset of patients, such as those with end-stage chronic kidney disease, heart failure, and coronary artery disease. Besides hypertension, atherosclerotic renovascular disease is responsible for several clinical manifestations, including life-threatening conditions, such as recurrent flash pulmonary edema, rapidly progressive chronic kidney disease, or acute kidney injury. Atherosclerotic renovascular disease is usually part of a more diffuse atherosclerotic process and requires a combination therapy including antihypertensive, antiplatelet and lipid-lowering agents, as well as optimization of antidiabetic treatment, if needed. Besides medical therapy, percutaneous renal angioplasty was supposed to be the most effective therapy for atherosclerotic renovascular disease, by leading to blood flow restoration. However, despite an apparently solid rationale, several randomized clinical trials failed to confirm the favorable effects of percutaneous renal angioplasty on blood pressure control, kidney function, cardiovascular and renal outcomes, previously reported in observational, retrospective and single-center cohorts, switching off the enthusiasm for this procedure. Several studies' limitations may partly account for this failure, including heterogeneity of diagnostic techniques, overestimation of the degree of renal artery stenosis, inappropriate timing of revascularization, multiple protocol revisions, frequent crossovers, and most importantly exclusion of patients at higher likelihood to respond to angioplasty. The purpose of this review is to summarize studies' potential weaknesses and provide guidance to the clinician for identification of patients who may benefit most from revascularization.

Revascularization for Renovascular Disease: A Scientific Statement From the American Heart Association.

Renovascular disease is a major causal factor for secondary hypertension and renal ischemic disease. However, several prospective, randomized trials for atherosclerotic disease failed to demonstrate that renal revascularization is more effective than medical therapy for most patients. These results have greatly reduced the generalized diagnostic workup and use of renal revascularization. Most guidelines and review articles emphasize the limited average improvement and fail to identify those clinical populations that do benefit from revascularization. On the basis of the clinical experience of hypertension centers, specialists have continued selective revascularization, albeit without a summary statement by a major, multidisciplinary, national organization that identifies specific populations that may benefit. In this scientific statement for health care professionals and the public-at-large, we review the strengths and weaknesses of randomized trials in revascularization and highlight (1) when referral for consideration of diagnostic workup and therapy may be warranted, (2) the evidence/rationale for these selective scenarios, (3) interventional and surgical techniques for effective revascularization, and (4) areas of research with unmet need.

Beyond Atherosclerosis and Fibromuscular Dysplasia: Rare Causes of Renovascular Hypertension.

Renovascular hypertension is one of the most common forms of secondary hypertension. Over 95% of cases of renovascular hypertension are due either to atherosclerosis of the main renal artery trunks or to fibromuscular dysplasia. These two causes of renal artery stenosis have been extensively discussed in recent reviews and consensus. The aim of the current article is to provide comprehensive and up-to-date information on the remaining causes. While these causes are rare or extremely rare, etiologic and differential diagnosis matters both for prognosis and management. Therefore, the clinician cannot ignore them. For didactic reasons, we have grouped these different entities into stenotic lesions (neurofibromatosis type 1 and other rare syndromes, dissection, arteritis, and segmental arterial mediolysis) often associated with aortic coarctation and other arterial abnormalities, and nonstenotic lesions, where hypertension is secondary to compression of adjacent arteries and changes in arterial pulsatility (aneurysm) or to the formation of a shunt, leading to kidney ischemia (arteriovenous fistula). Finally, thrombotic disorders of the renal artery may also be responsible for renovascular hypertension. Although thrombotic/embolic lesions do not represent primary vessel wall disease, they are characterized by frequent macrovascular involvement. In this review, we illustrate the most characteristic aspects of these different entities responsible for renovascular hypertension and discuss their prevalence, pathophysiology, clinical presentation, management, and prognosis.

Treino de Força Reduz Stress Oxidativo Cardíaco e Renal em Ratos com Hipertensão Renovascular / Strength Training Reduces Cardiac and Renal Oxidative Stress in Rats with Renovascular Hypertension

Resumo Fundamento O treino de força tem efeitos benéficos em doenças renais, além de ajudar a melhorar a defesa antioxidante em animais saudáveis. Objetivo Verificar se o treino de força reduz o dano oxidativo ao coração e rim contralateral para cirurgia de indução de hipertensão renovascular, bem como avaliar as alterações na atividade das enzimas antioxidantes endógenas superóxido dismutase (SOD), catalase (CAT) e glutationa peroxidase (GPx). Métodos Dezoito ratos machos foram divididos em três grupos (n=6/grupo): placebo, hipertenso e hipertenso treinado. Os animais foram induzidos a hipertensão renovascular através da ligação da artéria renal esquerda. O treino de força foi iniciado quatro semanas após a indução da hipertensão renovascular, teve 12 semanas de duração e foi realizada a 70% de 1RM. Depois do período de treino, os animais foram submetidos a eutanásia e o rim esquerdo e o coração foram retirados para realizar a quantificação de peróxidos de hidrogênio, malondialdeído e grupos sulfidrílicos, que são marcadores de danos oxidativos. Além disso, foram medidas as atividades das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase. O nível de significância adotado foi de 5% (p < 0,05). Resultados Depois do treino de força, houve redução de danos oxidativos a lipídios e proteínas, como pode-se observar pela redução de peróxidos de hidrogênio e níveis sulfidrílicos totais, respectivamente. Além disso, houve um aumento nas atividades das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase. Conclusão O treino de força tem o potencial de reduzir danos oxidativos, aumentando a atividades de enzimas antioxidantes. (Arq Bras Cardiol. 2021; 116(1):4-11)

Abstract Background Strength training has beneficial effects on kidney disease, in addition to helping improve antioxidant defenses in healthy animals. Objective To verify if strength training reduces oxidative damage to the heart and contralateral kidney caused by the renovascular hypertension induction surgery, as well as to evaluate alterations in the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) endogenous antioxidant enzymes. Methods Eighteen male rats were divided into three groups (n=6/group): sham, hypertensive, and trained hypertensive. The animals were induced to renovascular hypertension through left renal artery ligation. Strength training was initiated four weeks after the induction of renovascular hypertension, continued for a 12-weeks period, and was performed at 70% of 1RM. After the training period, the animals were euthanized and the right kidney and heart were removed for quantitation of hydroperoxides, malondialdehyde and sulfhydryl groups, which are markers of oxidative damage. In addition, the activity of SOD, CAT, and GPx antioxidant enzymes was also measured. The adopted significance level was 5% (p < 0.05). Results After strength training, a reduction in oxidative damage to lipids and proteins was observed, as could be seen by reducing hydroperoxides and total sulfhydryl levels, respectively. Furthermore, an increased activity of superoxide dismutase, catalase, and glutathione peroxidase antioxidant enzymes was observed. Conclusion Strength training is able to potentially reduce oxidative damage by increasing the activity of antioxidant enzymes. (Arq Bras Cardiol. 2021; 116(1):4-11)

[Efficacy of percutaneous transluminal renal angioplasty for pediatric renovascular hypertension: a meta-analysis].

Objective: To evaluate the efficacy and the related factors of percutaneous transluminal renal angioplasty (PTRA) for pediatric renovascular hypertension (RVH) by a systematic review and meta-analysis. Methods: A systematic search was performed on international and domestic databases (Pubmed, Excerpt Medical Database (EMBASE), Cochrane library, Clinical trial.gov, Medline, China Biology Medicine (CBM), China national knowledge infrastructure (CNKI), VIP database and Wanfang) which included studies on PTRA for pediatric RVH from the establishment of the databases to March 2019. Key words of "pediatric" "children" "renal artery stenosis" "renovascular hypertension" "angioplasty" and "intervention" were used. Meta-analysis was made on the rate of technical success, clinical blood pressure improvement, complication and restenosis of PTRA as well as the predictors of its efficacy. The data consolidation, analysis of heterogeneity and sensitivity, and publication bias were performed using Comprehensive meta analyst and Open meta analyst software. Results: Seventeen observational non-controlled studies comprising 384 patients with RVH who underwent PTRA were identified. The technical success rate of PTRA was 93.9% (95% confidence interval (CI) 89.3%-97.5%). The improvement rate of blood pressure was 68.4% (95%CI 57.2%-78.7%), and the cure rate was 40.0% (95%CI 25.0%-55.8%). The subsequent subgroup analysis showed that there was no significant difference in the improvement rate of blood pressure after PTRA among the patients with RVH caused by fibromuscular dysplasia, Takayasu arteritis and neurofibromatosis type 1, respectively (P>0.05). The improvement rate of blood pressure in patients with combined lesions in renal artery branches was significantly lower than that in patients with lesions only in main renal artery (RR=1.659, 95%CI 1.023-2.689, P=0.040). It was found that 25.5% (95% CI 19.3%-32.2%) of patients required repeat procedure because of restenosis of lesions. Procedural complication of PTRA occurred in 8.3% (95%CI 3.5%-14.4%) of patients. In terms of clinical blood pressure improvement rate after PTRA, there was heterogeneity among the enrolled studies, but the results of meta-analysis were robust with low risk of publication bias (t=1.690, 95%CI -0.363-3.124, P=0.110). Conclusion: The result of the Meta-analysis suggests that PTRA may provide a safe and effective treatment for pediatric RVH, and patients with stenosis of renal arterial branches are associated with relatively poor clinical outcomes.

Initial Estimated Glomerular Filtration Rate Decline and Long-Term Renal Function During Intensive Antihypertensive Therapy: A Post Hoc Analysis of the SPRINT and ACCORD-BP Randomized Controlled Trials.

Lowering blood pressure (BP) can lead to an initial decline in estimated glomerular filtration rate (eGFR). However, there is debate how much eGFR decline is acceptable. We performed a post hoc analysis of ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes-Blood Pressure) and SPRINT (Systolic Blood Pressure Intervention Trial), which randomized patients to intensive or standard systolic BP-targets. We determined the relation between initial decline in mean arterial pressure and eGFR. Subsequently, we stratified patients to BP-target and initial eGFR decrease and assessed the relation with annual eGFR decline after 1 year. A total of 13 266 patients with 41 126 eGFR measurements were analyzed. Up to 10 mm Hg of BP-lowering, eGFR did not change. Hereafter, there was a linear decrease of 3.4% eGFR (95% CI, 2.9%-3.9%) per 10 mm Hg mean arterial pressure decrease. The observed eGFR decline based on 95% of the subjects varied from 26% after 0 mm Hg to 46% with a 40 mm Hg mean arterial pressure decrease. There was no difference in eGFR slope (P=0.37) according to initial eGFR decline and BP-target, with a decrease of 1.24 (95% CI, 1.09-1.39), 1.20 (95% CI, 0.97-1.43), and 1.14 (95% CI, 0.77-1.50) in the 5%, 5% to 20%, and >20% stratum during intensive and 0.95 (95% CI, 0.81-1.09), 1.23 (95% CI, 0.97-1.49), and 1.17 (95% CI, 0.65-1.69) mL/minute per 1.73 m2 per year during standard treatment. In patients at high cardiovascular risk with and without diabetes mellitus, we found no association between initial eGFR and annual eGFR decline during BP-lowering treatment. Our results support that an eGFR decrease up to 20% after BP lowering can be accepted and suggest that the limit can be extended up to 46% depending on the achieved BP reduction. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000620, NCT01206062.

Hipertensão renovascular / Renovascular hypertension

Estenoses da artéria renal (EAS) é um estreitamento ou bloqueio de uma artéria para os rins. Pode causar insuficiência renal e pressão alta. Fumantes e ex-fumantes têm maior risco de contrair RAS. Os homens são afetados com essa condição duas vezes mais que as mulheres. É mais comum nas idades de 50 e 70. Colesterol alto, diabetes, excesso de peso e histórico familiar de doenças cardíacas também são fatores de risco para RAS. A pressão alta é uma causa e resultado do RAS. A causa mais comum de bloqueio da artéria renal é a arteriosclerose (espessamento e endurecimento das paredes da artéria) com acúmulo de colesterol e placa. Isso é semelhante ao que é visto nas artérias coronárias do coração, nas artérias carótidas, no cérebro e nos vasos das pernas. Apresentamos um caso de doença vascular renal em um homem diabético e ex-fumante e é apresentada uma atualização sobre a doença.

Renal artery stenoses (RAS) is a narrowing or blockage of an artery to the kidneys. It may cause kidney failure and high blood pressure. Smokers and ex-smokers have a greater risk of getting RAS. Men are affected with this condition twice as often as women. It>s most common in the ages of 50 and 70. High cholesterol, diabetes, being overweight, and having a family history of heart disease are also risk factors for RAS. High blood pressure is both a cause and a result of RAS. The most common cause of renal artery blockages is arteriosclerosis (the thickening and hardening of artery walls) with cholesterol and plaque build-up. This is similar to what is seen in the coronary arteries of the heart, the carotid arteries to the brain and the leg vessels.We presente a case of renal vascular disease in a diabetic and ex-smoker man and an up to date about the disease is presented.

Value of non-contrast-enhanced MR angiography combined with captopril renal scintigraphy in the diagnosis of renovascular hypertension / 中华核医学与分子影像杂志

Objective To evaluate the clinical value of non-contrast-enhanced MR angiography (NCE-MRA) combined with captopril renal scintigraphy (CRS) in the diagnosis of renovascular hypertension (RVH).Methods A total of 52 patients (33 males,19 females;age:(54.5±16.3) years) with highly suspected RVH between January 2018 and October 2018 from Henan Provincial People's Hospital were retrospectively analyzed.The examination data of NCE-MRA,basic renal dynamic imaging,CRS and digital subtraction angiography (DSA) were collected and reviewed.The renal artery stenosis (RAS) rate ≥70％ was the criterion for RVH diagnosed by DSA,which was considered as the gold standard.The diagnostic sensitivity,specificity,accuracy,positive predictive value (PPV) and negative predictive value (NPV) of NCE-MRA,CRS and NCE-MRA+CRS were determined.The consistency between NCE-MRA and DSA was analyzed by Kappa test.The differences of diagnostic efficiencies between CRS and NCE-MRA + CRS were compared by x2 test or Fisher exact test.Results There was a high consistency between NCE-MRA and DSA in the diagnosis of RVH (Kappa=0.81,95％ CI:0.62-0.96;P＜0.01).The diagnostic sensitivity,specificity,accuracy,PPV and NPV of NCE-MRA were 88.89％(24/27),92.00％(23/25),90.38％ (47/52),92.31％(24/26),and 88.46％(23/26) respectively,those of CRS were 81.48％(22/27),72.00％ (18/25),76.92％ (40/52),75.86％ (22/29) and 78.26％ (18/23) respectively,and those of NCE-MRA+CRS were 74.07％(20/27),100％(25/25),86.54％(45/52),100％(20/20) and 78.12％ (25/32) respectively.Compared with CRS,the specificity (P =0.01) and PPV (P =0.03) of NCE-MRA+CRS in the diagnosis of RVH were increased.Conclusion NCE-MRA and CRS are effective in the diagnosis of RVH,and the combination of two methods can significantly improve the diagnostic specificity and PPV than CRS alone.

Value of non-contrast-enhanced MR angiography combined with captopril renal scintigraphy in the diagnosis of renovascular hypertension / 中华核医学与分子影像杂志

Objective@#To evaluate the clinical value of non-contrast-enhanced MR angiography (NCE-MRA) combined with captopril renal scintigraphy (CRS) in the diagnosis of renovascular hypertension (RVH).@*Methods@#A total of 52 patients (33 males, 19 females; age: (54.5±16.3) years) with highly suspected RVH between January 2018 and October 2018 from Henan Provincial People′s Hospital were retrospectively analyzed. The examination data of NCE-MRA, basic renal dynamic imaging, CRS and digital subtraction angiography (DSA) were collected and reviewed. The renal artery stenosis (RAS) rate≥70% was the criterion for RVH diagnosed by DSA, which was considered as the gold standard. The diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of NCE-MRA, CRS and NCE-MRA+ CRS were determined. The consistency between NCE-MRA and DSA was analyzed by Kappa test. The differences of diagnostic efficiencies between CRS and NCE-MRA + CRS were compared by χ2 test or Fisher exact test.@*Results@#There was a high consistency between NCE-MRA and DSA in the diagnosis of RVH (Kappa=0.81, 95% CI: 0.62-0.96; P<0.01). The diagnostic sensitivity, specificity, accuracy, PPV and NPV of NCE-MRA were 88.89%(24/27), 92.00%(23/25), 90.38%(47/52), 92.31%(24/26), and 88.46%(23/26) respectively, those of CRS were 81.48%(22/27), 72.00%(18/25), 76.92%(40/52), 75.86%(22/29) and 78.26%(18/23) respectively, and those of NCE-MRA+ CRS were 74.07%(20/27), 100%(25/25), 86.54%(45/52), 100%(20/20) and 78.12%(25/32) respectively. Compared with CRS, the specificity (P=0.01) and PPV (P=0.03) of NCE-MRA+ CRS in the diagnosis of RVH were increased.@*Conclusion@#NCE-MRA and CRS are effective in the diagnosis of RVH, and the combination of two methods can significantly improve the diagnostic specificity and PPV than CRS alone.

Hipertensão arterial resistente (HAR) / Resistant arterial hypertension (RAH)

A hipertensão arterial resistente (HAR) é definida quando a pressão arterial (PA) permanece acima das metas recomendadas com o uso de três anti-hipertensivos de diferentes classes, incluindo um bloqueador do sistema renina- angiotensina (inibidor da enzima conversora da angiotensina [IECA] ou bloqueador do receptor de angiotensina [BRA]), um bloqueador dos canais de cálcio (BCC) de ação prolongada e um diurético tiazídico (DT) de longa ação em doses máximas preconizadas e toleradas, administradas com frequência, dosagem apropriada e comprovada adesão. Nesta definição está incluído o subgrupo de pacientes hipertensos resistentes, cuja PA é controlada com quatro ou mais medicamentos anti-hipertensivos, chamada de HAR controlada (HAR-C). A classificação da doença em HAR-C e HAR não controlada (HAR-NC), incluindo a HAR refratária (HAR-Ref), um fenótipo extremo de HAR-NC em uso de cinco ou mais anti-hipertensivos, é uma proposta que ganha espaço na literatura. Diante da suspeita clínica de HAR, é necessário verificar a confirmação diagnóstica, e a primeira etapa na investigação é a exclusão das causas de pseudorresistência, tais como falta de adesão ao tratamento (farmacológico e não farmacológico), posologia inadequada, técnica imprópria de aferição da PA e efeito do avental branco. O MAPA e o monitoramento residencial da pressão arterial (MRPA) são os exames para confirmação do controle inadequado da PA. Uma vez afastada a pseudorresistência, confirma-se a existência da HAR e inicia-se uma investigação diagnóstica com exames específicos, conforme a orientação das Diretrizes de Hipertensão em relação ao comprometimento de lesões em órgãos-alvo e hipertensão secundária. A ocorrência de comorbidades associadas deve ser detectada com exames especializados de acordo com a suspeita clínica. O objetivo do tratamento medicamentoso na HAR é detectar as causas do não controle e encontrar a melhor combinação de fármacos, visando o alcance das metas pressóricas com menor ocorrência de efeitos adversos e maior adesão. Em geral, busca-se otimizar o tratamento tríplice com os fármacos preferenciais, que são: IECA ou BRA, BCC di-hidropiridínico e DT.

Resistant hypertension (RHTN) is defined as blood pressure (BP) persistently above the recommended target values despite the use of three antihypertensive agents of different classes, including one blocker of the renin- angiotensin system (angiotensin-converting enzyme inhibitor [ACEI] or angiotensin receptor blocker [ARB]), one long- acting calcium channel blocker (CCB), and one long-acting thiazide diuretic (TD) at maximum recommended and tolerated doses, administered with appropriate frequency and doses and with proven adherence. The definition above includes a subgroup of patients with RHTN whose BP is controlled with four or more antihypertensive medications, known as controlled RHTN (C-RHTN). On clinical suspicion of RHTN, diagnostic confirmation is required, and the first step in the investigation is the exclusion of causes of pseudoresistance, such as lack of treatment adherence (pharmacological and non-pharmacological), inadequate dosing, improper BP measurement technique, and white-coat effect. Lack of BP control should be confirmed by ABPM and home blood pressure monitoring (HBPM). Secondary hypertension (SecH) is defined as increased BP due to an identifiable cause. Patients with RH should be investigated for the most prevalent causes of "non-endocrine" and "endocrine" SecH after exclusion of use of medications that may interfere with BP values: antiinflammatory drugs, glucocorticoids, nasal decongestants, appetite suppressants, antidepressants, immunosuppressants, erythropoietin, contraceptives, and illicit drugs. The objective of pharmacological treatment in RHTN is to identify the causes of lack of control and find the best combination of drugs, aiming at achieving the target BP with few adverse effects and greater adherence. In general, triple treatment optimization is attempted with preferred drugs, namely, ACEIs or ARBs, dihydropyridine CCBs, and TDs

Effect of chrysanthemum extract on myocardial fibrosis in rats with renovascular hypertension.

OBJECTIVE: To investigate the inhibitory effect of chrysanthemum extract on myocardial fibrosis in rats with renovascular hypertension, and explore the possible mechanism underlying this effect. METHODS: Sixty Wistar rats were randomly divided into six groups: sham operation, model, positive control, and low-, medium-, and high-dose Huai chrysanthemum extract groups (ten rats per group). With the exception of the sham operation group, a renal hypertensive model was established in rats using the ""two-kidney, one clip"" method. After 6 weeks, low-, medium-, and high-dose groups were intragastrically administered chrysanthemum extract at 1, 2, or 4 g/kg, respectively, once daily for 4 weeks. The positive control group was administered Kato Pury at 50 mg/kg once daily for 4 weeks, while sham operation and model groups received an equal volume of distilled water once daily for 4 weeks. Blood pressure changes were examined before modeling, 6 weeks after modeling, and after 4 weeks of treatment administration. Ventricular remodeling indexes were measured by high frequency echocardiography after 4 weeks of treatment administration. Pathological changes were observed by hematoxylin and eosin, and Masson's trichrome staining methods. Collagen typeⅠ (Col Ⅰ) and type Ⅲ (Col Ⅲ) expression were examined by enzyme-linked immunosorbent assays. Transforming growth factor-ß1 (TGF-ß1), sma mad 3 (Smad3), Smad7, Ras homolog gene family, member A (RhoA), and Rho-associated protein kinase 1 (ROCK1) protein expression were detected by Western blot. RESULTS: Compared with the model group, chrysanthemum-administered groups and the positive control group showed significant improvement of arterial blood pressure, echocardiography indicators, and degree of myocardial fibrosis (P < 0.05). In addition, these groups exhibited decreased expression of Col Ⅰ, Col Ⅲ, RhoA, ROCK1, TGF-ß1, and Smad3, and increased Smad7 expression. Such improvements were most obvious in the high-dose chrysanthemum extract group (P < 0.05). CONCLUSION: Chrysanthemum extract could effectively reduce myocardial fibrosis in rats with renovascular hypertension by a mechanism that potentially involves inhibition of RhoA/ROCK1 and TGF-ß1/Smad signaling pathways.

Direct Recording of Cardiac and Renal Sympathetic Nerve Activity Shows Differential Control in Renovascular Hypertension.

There is increasing evidence that hypertension is initiated and maintained by elevated sympathetic tone. Increased sympathetic drive to the heart is linked to cardiac hypertrophy in hypertension and worsens prognosis. However, cardiac sympathetic nerve activity (SNA) has not previously been directly recorded in hypertension. We hypothesized that directly recorded cardiac SNA levels would be elevated during hypertension and that baroreflex control of cardiac SNA would be impaired during hypertension. Adult ewes either underwent unilateral renal artery clipping (n=12) or sham surgery (n=15). Two weeks later, electrodes were placed in the contralateral renal and cardiac nerves to record SNA. Baseline levels of SNA and baroreflex control of heart rate and sympathetic drive were examined. Unilateral renal artery clipping induced hypertension (mean arterial pressure 109±2 versus 91±3 mm Hg in shams; P<0.001). The heart rate baroreflex curve was shifted rightward but remained intact. In the hypertensive group, cardiac sympathetic burst incidence (bursts/100 beats) was increased (39±14 versus 25±9 in normotensives; P<0.05), whereas renal sympathetic burst incidence was decreased (69±20 versus 93±8 in normotensives; P<0.01). The renal sympathetic baroreflex curve was shifted rightward and showed increased gain, but there was no change in the cardiac sympathetic baroreflex gain. Renovascular hypertension is associated with differential control of cardiac and renal SNA; baseline cardiac SNA is increased, whereas renal SNA is decreased.

Revascularization in a 17-Year-Old Girl with Neurofibromatosis and Severe Hypertension Caused by Renal Artery Stenosis.

Renal artery stenosis caused by neurofibromatosis is a rare cause of renovascular hypertension. This hypertension can develop during childhood and is one of the leading causes of poor outcome. We report the case of a 17-year-old girl who was incidentally diagnosed with severe hypertension. During her examination for secondary hypertension, we reached a diagnosis of neurofibromatosis type 1 on the basis of a cluster of typical findings: optic nerve glioma, café au lait spots, nodular neurofibromas, and axillary freckling. Renal angiograms revealed a hemodynamically significant left renal artery stenosis (70%). Renal angioplasty with a self-expanding stent was performed one month later for rapidly progressive renal artery stenosis (90%) and uncontrolled blood pressure. Excellent blood pressure control resulted immediately and was maintained as of the 2-year follow-up evaluation. We think that percutaneous transluminal renal angioplasty can be effective in select patients who have neurofibromatosis type 1 and refractory hypertension caused by renal artery stenosis.

Effects of Percutaneous Transluminal Renal Angioplasty on Office and Home Blood Pressure and Home Blood Pressure Variability in Hypertensive Patients With Renal Artery Stenosis.

This study included 126 hypertensive patients with renal artery stenosis (mean age, 63 years; 22.2% fibromuscular dysplasia [FMD]) and investigated the effects of percutaneous transluminal renal angioplasty on office and home blood pressure (BP), and BP variability estimates derived from home BP, both at baseline and up to 12 months after angioplasty. Home BP was measured for 7 consecutive days, and the threshold defining uncontrolled home BP was ≥135/85 mm Hg. In both the FMD and atherosclerotic stenosis (ARAS) groups, office and home BP decreased significantly after angioplasty (all P<0.01), but the decrease in morning home (-22±19 versus -10±20 mm Hg; P<0.01) but not in office (-32±24 versus -23±28 mm Hg; P=0.11) systolic BP at 12 months was significantly greater in FMD. In both groups, all morning BP variability indices except the coefficient of variation in ARAS decreased significantly after revascularization (all P<0.05 by repeated-measures ANOVA). The decrease in all morning systolic BP variability estimates was greater for FMD than for ARAS (all P<0.05 by 2-way repeated-measures ANOVA), with the exception of variability independent of the mean (P=0.11). The prevalence of uncontrolled home BP was 77.0% at baseline and 38.9% after revascularization. Duration of hypertension (odds ratio, 1.48), ARAS (odds ratio, 3.18), and the presence of proteinuria (odds ratio, 2.10) were independent predictors of uncontrolled home BP after revascularization (all P<0.05). In conclusion, renal angioplasty produced a greater decrease of morning home systolic BP in FMD; however, in both groups, it decreased BP variability irrespective of BP response. Measurement of home BP seems to be important for treatment success, especially in ARAS.

Successful Treatment of Resistant Hypertension by Means of Chronic Renal Artery Occlusion Revascularization in a Fragile Patient.

BACKGROUND: Renal artery stenosis is a common cause of secondary hypertension refractory to medical therapy. Percutaneous angioplasty along with metallic stent placement has been described as an effective treatment for revascularization of the renal artery. CASE REPORT: A 54-year-old woman affected by paranoid schizophrenia with a history of hypertension and chronic renal failure due to renal artery occlusion was treated by endovascular recanalization and stent placement that resulted in improvement of renal function and control of hypertension. Laboratory studies 4 months after the revascularization revealed blood creatinine decrease gradually from 8.57 mg/dL to 3 mg/dL. CONCLUSIONS: Revascularization with stenting has proven to be a safe and effective procedure in the treatment of total renal artery occlusion which also led to a significant relief at a psychological level.

NADPH oxidase in the renal microvasculature is a primary target for blood pressure-lowering effects by inorganic nitrate and nitrite.

Renal oxidative stress and nitric oxide (NO) deficiency are key events in hypertension. Stimulation of a nitrate-nitrite-NO pathway with dietary nitrate reduces blood pressure, but the mechanisms or target organ are not clear. We investigated the hypothesis that inorganic nitrate and nitrite attenuate reactivity of renal microcirculation and blood pressure responses to angiotensin II (ANG II) by modulating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and NO bioavailability. Nitrite in the physiological range (10(-7)-10(-5) mol/L) dilated isolated perfused renal afferent arterioles, which were associated with increased NO. Contractions to ANG II (34%) and simultaneous NO synthase inhibition (56%) were attenuated by nitrite (18% and 26%). In a model of oxidative stress (superoxide dismutase-1 knockouts), abnormal ANG II-mediated arteriolar contractions (90%) were normalized by nitrite (44%). Mechanistically, effects of nitrite were abolished by NO scavenger and xanthine oxidase inhibitor, but only partially attenuated by inhibiting soluble guanylyl cyclase. Inhibition of NADPH oxidase with apocynin attenuated ANG II-induced contractility (35%) similar to that of nitrite. In the presence of nitrite, no further effect of apocynin was observed, suggesting NADPH oxidase as a possible target. In preglomerular vascular smooth muscle cells and kidney cortex, nitrite reduced both basal and ANG II-induced NADPH oxidase activity. These effects of nitrite were also abolished by xanthine oxidase inhibition. Moreover, supplementation with dietary nitrate (10(-2) mol/L) reduced renal NADPH oxidase activity and attenuated ANG II-mediated arteriolar contractions and hypertension (99±2-146±2 mm Hg) compared with placebo (100±3-168±3 mm Hg). In conclusion, these novel findings position NADPH oxidase in the renal microvasculature as a prime target for blood pressure-lowering effects of inorganic nitrate and nitrite.

Effect of Telmisartan on Myocardial Remodeling in Rats with Renovascular Hypertention / 医药导报

Objective To investigate the the molecular mechanism of telmisartan for myocardial remodeling in rats with renovascular hypertention. Methods The renovascular hypertensive myocardial hypertrophy model of rats were established by narrowing the left renal artery.The total of 45 mature male SD rats were divided into sham-operated group(n= 15),model control (n = 15 ) and telmisartan group ( n = 15 ) randomly. The rats in telmisartan group were treated with telmisartan (10 mg?kg-1?d-1 ) while those in the sham-operated and model control were reated with the same amounts of distilled water by intragastrical administration . At 8th week of administration, the myocardial structure and function were detected by ultrasonography.The blood pressure was measured by arterial catheterization and calculating the left ventricular mass index (LVMI) .The level of serum calcium and nerve phosphatase ( CaN) and the expression of β-myosin heavy chain ( β-MHC) mRNA were detected. Results The thickness of left ventricular,ejection fraction[(69.23± 1.09)% vs(73.77± 3.00)%], fractional shortening [(30.21±2.02)% vs(35.29±0.90)%],LVMI[(2.83±0.14) mg?g-1 vs(2.32±0.11) mg?g-1 ] were decreased,and the differences were statistically significant (P<0.05).The level of serum calcium and nerve phosphatase (CaN) and the expression of β-myosin heavy chain (β-MHC) mRNA were decreased in telmisartan treated rats,and the differences were statistically significant (P< 0.05) when compared with the model control group. Conclusion Telmisartan can improve the myocardial hypertrophy of renovascular hypertensive rats,and it may downregulate the expression of β-MHC by inactivating of the start signal CaN and its downstream signal pathway.

Preserved function of late-outgrowth endothelial cells in medically treated hypertensive patients under well-controlled conditions.

Endothelial progenitor cells (EPCs) participate in renal repair, but their number and function may be impaired by exposure to cardiovascular risk factors. The number of circulating EPCs is decreased in essential and renovascular hypertensive patients, but the effects of hypertension on EPC function are incompletely understood. We hypothesized that EPC function was preserved under well-controlled conditions in treated hypertensive patients. Patients with atherosclerotic renal artery stenosis (ARAS; n=22) or essential hypertension (n=24) were studied during controlled sodium intake and antihypertensive regimen. Late-outgrowth EPCs were isolated from the inferior vena cava (IVC) and renal vein blood of ARAS and essential hypertension patients and a peripheral vein of matched normotensive controls (n=18). The angiogenic function of EPCs was assessed in vitro, and multidetector computed tomography was used to measure single-kidney hemodynamics and function in ARAS and essential hypertension patients. Inflammatory biomarkers and EPC homing signal levels and renal release were calculated. Inferior vena cava and renal vein-obtained EPC function were similar in ARAS and essential hypertension patients and comparable to that in normal controls (tube length, 171.86±16.846, 191.09±14.222, 174.925±19.774 µm, respectively). Function of renal vein-obtained EPCs directly correlated with stenotic kidney glomerular filtration rate, EPC homing factors, and anti-inflammatory mediator levels in ARAS patients. Therefore, EPC function was relatively preserved in ARAS patients, although it directly correlated with renal function. Adequate EPC function supports the feasibility of using autologous EPCs as a therapeutic option in essential and renovascular hypertensive patients. Homing signals and inflammatory mediators may potentially regulate EPC angiogenic function.