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.

Posterior Reversible Encephalopathy Syndrome in a Child With Renovascular Hypertension.

A 6-year-old child presented with headache for 1 month and seizures followed by altered consciousness for 1 day. He had new-onset daily occipital headache for 1 month of mild to moderate severity and pulsating character. What is your diagnosis?

Defining Hemodynamic Significance of Renal Artery Stenosis: Insights From a Porcine Model of Graded Renal Artery Stenosis.

RATIONALE AND OBJECTIVES: To investigate the renal pressure-flow relationship and its relation to renin release, because the renal perfusion pressure below which renal flow starts to decline and renin secretion is upregulated is unclear. MATERIALS AND METHODS: A porcine model of graded unilateral renal artery stenosis was created. The severity of the stenosis was expressed as the ratio between distal renal pressure (Pd) and aortic pressure (Pa). Pd and renal flow velocity were continuously measured using a combined pressure-flow wire (Combowire®). Hemodynamic measurements and blood sampling for renin, angiotensin and aldosterone were performed in baseline conditions and during progressive balloon inflation in the renal artery leading to Pd decrease per 5% increment. Resistive index (RI) was computed as (1 - (End Diastolic V/Peak Systolic V))*100. RESULTS: For a 5% decrease in renal perfusion pressure (95% of aortic pressure or 5% decrease compared to Pa), peak systolic velocity started to decrease. A significant decrease in average peak flow velocity was observed when distal renal perfusion pressure decreased by 25% and was associated with activation of ipsilateral renin secretion. The RI decreased already for minimal changes in Pd/Pa ratio. CONCLUSION: In an animal model of unilateral graded renal artery stenosis, a 25% decrease in perfusion pressure results in a significant decrease in distal renal flow, causing upregulation of renin secretion.

IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension.

Extracellular vesicles (EVs) obtain properties of immunomodulation and tissue repair from their parental mesenchymal stem cells (MSCs), and upon delivery may be associated with fewer adverse events. EVs derived from adipose-tissue MSCs restored kidney function by attenuating kidney inflammation in a swine model of metabolic syndrome (MetS) and renal artery stenosis via anti-inflammatory pathways. EVs also ameliorated myocardial injury in renovascular hypertension (RVH) secondary to inflammation in cardiorenal disease, but the mechanisms regulating this effect are unknown. We hypothesize that the anti-inflammatory cytokine interleukin (IL)-10 mediates the reparative effects of EVs on cardiovascular complications in a preclinical swine model with coexisting MetS and RVH. Twenty-three pigs established as Lean controls or RVH models were observed for 16 weeks. At 12 weeks RVH subgroups received an intrarenal delivery of 1011 either wildtype (WT) EVs or EVs after IL-10 knockdown (KD) (RVH+WT-EVs or RVH+IL-10-KD-EVs, respectively). Cardiac and renal function were studied in-vivo and myocardial tissue injury in-vitro 4 weeks later. RVH pigs showed myocardial inflammation, fibrosis, and left ventricular diastolic dysfunction. WT-EVs attenuated these impairments, increased capillary density, and decreased myocardial inflammation in-vivo. In-vitro, co-incubation with IL-10-containing WT-EVs decreased activated T-cells proliferation and endothelial cells inflammation and promoted their migration. Contrarily, these cardioprotective effects were largely blunted using IL-10-KD-EVs. Thus, the anti-inflammatory and pro-angiogenic effects of EVs in RVH may be partly attributed to their cargo of anti-inflammatory IL-10. Early intervention of IL-10-containing EVs may be helpful to prevent cardiovascular complications of MetS concurrent with RVH.

Revascularization for controlling hypertension and improving cardiorenal failure in Leriche syndrome.

Leriche syndrome usually occurs when atherosclerotic obstructions result in luminal narrowing of the abdominal aorta or iliac arteries and leads to thrombosis; it rarely causes heart or renal failure. We report the case of a 58-year-old Asian man with heart and renal failure as the dominant clinical manifestations of renovascular hypertension caused by Leriche syndrome. We performed an aorto-bifemoral bypass and unilateral renal artery stenting. Post-operative echocardiography showed improved cardiac function, with the left ventricular ejection fraction increasing from 30% before surgery to 54.2% after surgery. Moreover, his heart rate and blood pressure became stable, and his serum creatinine and brain natriuretic peptide levels decreased from 3.46 to 1.08 mg/dL and 685 to 4 pg/mL, respectively. Our case report shows that aorto-bifemoral bypass and unilateral renal artery stenting can effectively treat heart and renal failure resulting from renovascular hypertension caused by Leriche syndrome.

Intracranial Pressure During the Development of Renovascular Hypertension.

[Figure: see text].

Renovascular Hypertension Induces Myocardial Mitochondrial Damage, Contributing to Cardiac Injury and Dysfunction in Pigs With Metabolic Syndrome.

BACKGROUND: Renovascular hypertension (RVH) often manifest with metabolic syndrome (MetS) as well. Coexisting MetS and hypertension increases cardiovascular morbidity and mortality, but the mechanisms underlying cardiac injury remain unknown. We hypothesized that superimposition of MetS induces myocardial mitochondrial damage, leading to cardiac injury and dysfunction in swine RVH. METHODS: Pigs were studied after 16 weeks of diet-induced MetS with or without RVH (unilateral renal artery stenosis), and Lean controls (n = 6 each). Systolic and diastolic cardiac function were assessed by multidetector CT, and cardiac mitochondrial morphology (electron microscopy) and myocardial function in tissue and isolated mitochondria. RESULTS: Body weight was similarly higher in MetS groups vs. Lean. RVH groups achieved significant stenosis and developed hypertension. Mitochondrial matrix density and adenosine triphosphate production were lower and H2O2 production higher in RVH groups vs. Lean and MetS. Lean + RVH (but not MetS + RVH) activated mitophagy, which was associated with decreased myocardial expression of mitophagy-related microRNAs. MetS groups exhibited higher numbers of intermitochondrial junctions, which could have prevented membrane depolarization/activation of mitophagy in MetS + RVH. Cardiac fibrosis, hypertrophy (increased left ventricular muscle mass), and diastolic function (decreased E/A ratio) were greater in MetS + RVH vs. Lean + RVH. CONCLUSIONS: MetS+RVH induces myocardial mitochondrial damage and dysfunction. MetS + RVH failed to activate mitophagy, resulting in greater cardiac remodeling, fibrosis, and diastolic dysfunction. Mitochondrial injury and impaired mitophagy may constitute important mechanisms and therapeutic targets to ameliorate cardiac damage and dysfunction in patients with coexisting MetS and RVH.

Spontaneous Neuronal Plasticity in the Contralateral Motor Cortex and Corticospinal Tract after Focal Cortical Infarction in Hypertensive Rats.

OBJECTIVES: In this study, we investigated the spontaneous neural plasticity on the contralateral side in hypertensive rats, including the expression of nerve growth factors (synaptophysin [SYN] and growth-associated protein 43 [GAP-43]), and the association between nerve fiber sprouting and redistribution, and the recovery of motor functions following sensorimotor cortical infarction. METHODS: Initially, Sprague-Dawley rats were induced with renal hypertension by the bilateral renal arteries clips method. Further, they were induced with cerebral ischemia by the middle cerebral artery electrocoagulation method; 70 male rats completed the study. We compared the changes in the corticospinal tract (CST) and the expressions of SYN and GAP-43 on the contralateral side in rats with cerebral infarction using immunohistochemical staining, western blot, and biotinylated dextran amine (BDA) tracing analyses. The recovery of motor function in rats after cortical infarction was evaluated by the foot-fault and beam-walk tests. RESULTS: The motor behavior tests revealed that the motor function of rats could recover to various degrees after focal cortical infarction. Compared with the sham-operated group, the SYN and GAP-43 levels increased in the motor cortex of the opposite hemisphere within 28 days after middle cerebral artery occlusion (MCAO). The increase in SYN and GAP-43 expressions presented differently in layers Ⅱ, Ⅲ, and Ⅴ. The amount of BDA-positive fibers also increased significantly in the denervated cervical spinal gray matter on day 56 post-MCAO. CONCLUSIONS: The increases in SYN and GAP-43 on the contralateral side of the motor cortex could promote CST sprouting and rewiring in the spinal cord gray matter and also spontaneous motor function recovery after cortical infarction.

Myrtus communis improves cognitive impairment in renovascular hypertensive rats.

Myrtus communis has anti-inflammatory, neuroprotective and anticholinesterase activities yet there have been limited studies examining effects of Myrtus communis on cognitive functions. This study investigated the possible effects of Myrtus communis on changes in the cognitive functions of experimental renovascular hypertensive rats. Fifty-six Wistar-Albino rats were equally divided into 4 groups; sham-operated control, renovascular hypertension (RVH), ramipril (RVH + Ram) and Myrtus communis extract (RVH + MC) treatment groups. Goldblatt's 2-kidney 1-clip (2K1C) method was used to induce RVH. At the end of 9 weeks of treatment, after blood pressure recording, the animals underwent new object recognition test and Morris water maze (MWM) task. Following these tests, blood brain barrier (BBB) integrity was examined in 6 animals from each group. In the others after decapitation, osteopontin and interleukin (IL)-10 levels were measured in blood samples; while matrix metalloproteinase (MMP)-13, sodium potassium adenosine triphosphatase (Na+,K+-ATPase), cluster of differentiation (CD) 36, amyloid beta (Aß), neprilysin levels, and acetylcholinesterase (AChE) activity were investigated in hippocampal tissues. In RVH group, high systolic blood pressure decreased serum IL-10 levels, increased serum osteopontin levels and also impaired BBB permeability. Hippocampal MMP-13, CD36, Aß, neprilysin levels and AChE activities were elevated, while there were decreases in Na+,K+-ATPase levels. In new objet recognition test, discrimination index (DI) was determined as lower in saline-treated RVH group compared to control animals. In MWM training trail, 4th day performance in finding platform was significantly reduced in saline-treated RVH group compared to control group. RVH also decreased the time spent in target quadrant in probe test of MWM task compared to control group. In both of the treatment groups, all biochemical parameters were restored in parallel with improvement in the behavioral test performances. The results of this study suggest that Myrtus communis extract may improve the cognitive dysfunctions in hypertension through antihypertensive, anti-inflammatory and anticholinesterase activities.

Correlations Between Interleukin-11 Expression and Hypertensive Kidney Injury in a Rat Model of Renovascular Hypertension.

BACKGROUND: Interleukin-11 (IL-11) is a pleiotropic cytokine of the interleukin-6 family. Recent studies revealed its crucial role in the development of cardiovascular fibrosis. In this study we examined IL-11 expression levels in the heart and the kidney exposed to high blood pressure in renovascular hypertensive rats and their correlations to fibrotic markers and kidney injury. METHODS: Two-kidney, one-clip renovascular hypertension (2K1C) was induced in rats. IL-11 expression was measured by real-time polymerase chain reaction in the left ventricle and the right kidney. The correlation of cardiac IL-11 expression with biomarkers of renal fibrosis was assessed. We further investigated IL-11 expression in 2K1C rats grouped into rats with malignant vs. nonmalignant hypertension (distinguishing criteria: weight loss, number of fibrinoid necrosis, and onion skin lesions). RESULTS: Thirty-five days after clipping, mean arterial pressure was significantly increased in 2K1C. Renal IL-11 expression was elevated in 2K1C. In the heart there was only a trend toward higher IL-11 expression in 2K1C. IL-11 in the kidney in 2K1C correlated with the expression of transforming growth factor (TGF)-ß1/2, collagens, fibronectin, osteopontin, as well as tissue inhibitors of metalloprotease 1/2. There were also correlations of IL-11 with tissue collagen expansion, number of activated fibroblasts and serum creatinine, but no correlation with mean arterial pressure. Renal expression of IL-11 was highest in rats with malignant hypertension. CONCLUSIONS: Renal IL-11 expression of renovascular hypertensive rats is markedly increased and correlates with profibrotic markers and loss of function and might therefore serve as a biomarker for the severity of hypertensive nephrosclerosis.

Successful Depressor Effect Concomitant with Complete Normalization of High Renin and Aldosterone Profile by Percutaneous Transluminal Renal Angioplasty in a Patient with Acute Exacerbated Heart Failure with Preserved Ejection Fraction.

BACKGROUND Although the effect of percutaneous transluminal renal angioplasty (PTRA) on clinical outcomes has not been established in previous clinical studies, some case reports showed that PTRA drastically improved patient outcomes. The appropriateness of PTRA should be discussed in detail. CASE REPORT A 59-year-old man had been on treatment for hypertension for 5 years, but his blood pressure (BP) had been poorly controlled for the past 5 months. He was hospitalized for pulmonary edema due to heart failure with preserved ejection fraction (HFpEF). During hospitalization, ultrasound and plain computed tomography revealed atrophy of the right kidney, and laboratory investigations indicated secondary aldosteronism with high plasma renin activity (PRA). Unenhanced magnetic resonance imaging (MRI) suggested severe stenosis or occlusion of the right renal artery. PTRA was performed for total occlusion at the origin of the right renal artery, resulting in favorable dilation of the vessel and good blood flow. A differential renal vein renin assay showed a right-left difference of PRA before PTRA, but this disappeared after the procedure. Both PRA and the plasma aldosterone concentration were normalized after PTRA. In addition, the patient's BP decreased, proteinuria was reduced, diuretics could be discontinued, and his calcium channel blocker dosage was decreased. CONCLUSIONS The present case suggests that screening for renal artery stenosis by unenhanced MRI may be useful in patients who have HFpEF because PTRA can be used to achieve marked improvement of hypertension, endocrine abnormalities, and heart failure if stenosis is detected.

Secondary Hypertension and Complications: Diagnosis and Role of Imaging.

Hypertension is a common problem; if left untreated, it can result in significant complications, including those involving the cardiovascular system and end organs. Approximately 10% of patients with hypertension are classified as having secondary hypertension, defined as hypertension attributable to a specific and potentially remediable cause. The evaluation for secondary hypertension typically begins with acquiring the patient history and performing a physical examination and screening laboratory tests. Directed imaging may be performed, on the basis of laboratory test results, to assess for potential causes of secondary hypertension. The causes can be broadly classified as endocrine (eg, hyperaldosteronism, pheochromocytoma, hyperparathyroidism) and nonendocrine (eg, aortic coarctation, renal vascular hypertension). In addition, patients with hypertension can develop significant complications that also are diagnosed with imaging, including conditions involving the cardiovascular system (eg, aortic aneurysm, acute aortic syndrome) and central nervous system (eg, stroke, subarachnoid hemorrhage, and posterior reversible encephalopathy syndrome). The imaging workup and imaging appearances of some of the causes of secondary hypertension are reviewed, treatment options are discussed, and the imaging appearances of hypertension-related complications are described. It is important for radiologists to accurately diagnose the secondary causes of hypertension, as many of them are treatable, and treatment may result in improved symptoms or resolution of hypertension. ©RSNA, 2019.

Renovascular Hypertension Aggravates Atherosclerosis in Cholesterol-Fed Rabbits.

BACKGROUND: Hypertension is a major risk factor for atherosclerotic disease. However, it is still not clear whether mechanical stress caused by hypertension directly affects the atherosclerotic development in the aorta and coronary arteries. OBJECTIVES AND METHODS: We generated a hypertensive (HTN) rabbit model by surgical removal of the left kidney and partial ligation of the right renal artery. After a 16-week cholesterol diet, we compared aortic and coronary atherosclerosis of HTN rabbits with those of normotensive rabbits. RESULTS: Hypertension did not affect lipid and apolipoprotein levels in plasma but led to a 3.0-fold increase in aortic atherosclerosis and a 1.7-fold increase in coronary atherosclerosis compared with control rabbits. Enhanced atherosclerosis in HTN rabbits was caused by significant increases in macrophages and smooth muscle cells in the lesions. Furthermore, oxidized LDL contents in the lesions were significantly increased in HTN rabbits. In addition, HTN rabbits exhibited prominent hyaline arteriolosclerosis in coronary arterioles. CONCLUSIONS: These results indicate that hyper tension not only enhances atherosclerosis in large arteries including the aorta and coronary arteries but also affects hyaline arteriolosclerosis in small arteries.

Nephrotic range proteinuria and metabolic alkalosis in Takayasu arteritis.

Nephrotic range proteinuria and metabolic alkalosis are unusual findings in large vessel vasculitis. In this case, renovascular hypertension with unilateral renal artery stenosis in Takayasu arteritis was complicated by nephrotic range proteinuria. Symptoms resolved after angioplasty, although non-nephrotic proteinuria persisted. The renal pathology of Takayasu arteritis included focal glomerulosclerosis.

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.

An infant case of renovascular hypertension in moyamoya disease treated by angioplasty.

Guo J, Guo L, Zeng G, Tong Z, Gao X, Gu Y. An infant case of renovascular hypertension in moyamoya disease treated by angioplasty. Turk J Pediatr 2018; 60: 331-334. Here we report the treatment experience of an 18-month-old female infant case of renovascular hypertension due to moyamoya disease by angioplasty. Although renal blood flow was recovered immediately after operation, 12 months follow-up found severe restenosis which required us to perform a right renal autotransplantation.

Moderate-intensity exercise and renin angiotensin system blockade improve the renovascular hypertension (2K1C)-induced gastric dysmotility in rats.

Actually, arterial hypertension is a major public health concern, which involves the renin angiotensin aldosterone system (RAS), via activation of the angiotensin receptors AT1 and AT2 of the cardiovascular system. Although angiotensin is an important stimulant of the gut permeability to sodium and water, little is known about the effects of arterial hypertension on gut motor behavior. Thus, we evaluated in rats the effect of hypertension induced by two-kidney one-clip (2K1C) model on the gastric motility, as well as the influence of exercise and RAS blockers treatment in such phenomenon. One week after surgery the rats were treated with Aliskiren (50 mg·kg-1, p.o.), Captopril (50 mg·kg-1, p.o.) or Losartan (10 mg·kg-1, p.o). Other group of rats was submitted to swimming with 5% body weight overload. After 4 weeks of physical training or pharmacological treatment, we assessed the gastric retention in all groups (GR) of a liquid test meal, the mean arterial pressure (MAP), the heart rate (HR) and the HR variation (HRV) as well as the in vitro contractility of gastric fundus. Renovascular hypertension increased (p < 0.05) the GR, MAP and HR, a phenomenon prevented by pretreatment with RAS blockers or exercise. The two kidney one-clip Hypertension (2K1C) decreased (p < 0.05) the gastric fundus responsiveness, a phenomenon also prevented by exercise. It conclusion, renovascular hypertension delays the gastric emptying of liquids, a phenomenon involving the activation of RAS, where exercise or blockade with aliskiren, captopril and losartan prevent gastric dysmotility.

Ccl2 deficiency protects against chronic renal injury in murine renovascular hypertension.

Inflammation plays an important role in the pathogenesis of renal and cardiovascular disease in renovascular hypertension (RVH). Ccl2 is an important mediator of inflammation, and is induced within 24 hours following surgery to establish RVH in the murine 2 kidney 1 clip model, a time prior to onset of interstitial inflammation, fibrosis, or tubular atrophy. We tested the hypothesis that Ccl2 deficiency protects the stenotic kidney (STK) from development of chronic renal damage in mice with renovascular hypertension due to renal artery stenosis (RAS). RAS surgery was performed on wild type (WT) and Ccl2 knock out (KO) mice; animals were studied for four weeks. Renal blood flow was reduced to similar extent in both WT and Ccl2 KO mice with RVH. Perfusion of the stenotic kidney was significantly reduced in Ccl2 KO mice as assessed by magnetic resonance imaging (MRI). Stenotic kidney volume in WT, but not in Ccl2 KO mice, was significantly reduced following surgery. Cortical hypoxia was observed in the stenotic kidney of Ccl2 KO mice, as assessed by blood oxygen level-dependent MRI (BOLD-MRI). Ccl2 KO mice showed less cortical atrophy than WT RAS mice. Ccl2 deficiency reduced the number of infiltrating mononuclear cells and expression of Ccl5, Ccl7, Ccl8, Ccr2 and Cd206. We conclude that Ccl2 is a critical mediator of chronic renal injury in RVH.