Importance of Awareness and Careful Follow-Up of Suspected IgG4-Related Periaortitis.

IgG4-related disease may cause large vessel vasculitis, which often affects males in their 60s. Here, we report a case of suspected IgG4-related periaortitis in a 76-year-old man with lower left-side chest pain and hypertension based on computed tomography findings of thickened lesions surrounding the abdominal aorta and mesenteric arteries after ruling out acute cardiovascular diseases. His serum IgG4 levels were high, but the C-reactive protein and D-dimer levels were within normal limits. Because IgG4-related periaortitis was suspected, the patient was carefully monitored for blood pressure control, inflammatory markers, and renal function. Steroid therapy was not initiated, however, due to the difficulties performing a biopsy targeting periaortitis to obtain a definitive diagnosis and possible severe complications. During follow-up observation, IgG4-related kidney disease was suspected based on a slight increase in the serum creatinine levels and a renal biopsy was considered. Just before performing the renal biopsy, we observed left renal hydronephrosis caused by spreading retroperitoneal fibrosis. Immediate ureteral stent implantation and initiation of steroid therapy successfully improved the renal function and decreased the serum IgG4 level, respectively. Although relatively rare, IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis should be considered in the differential diagnosis of aortic diseases, even after ruling out serious major acute cardiovascular diseases. Cardiologists should also be aware of the possible progression and systemic spread of this disease.

Transient receptor potential vanilloid 1-expressing cardiac afferent nerves may contribute to cardiac hypertrophy in accompany with an increased expression of brain-derived neurotrophic factor within nucleus tractus solitarius in a pressure overload model.

INTRODUCTION: Increased sympathetic output contributes to cardiac hypertrophy. Sympathoexcitation is induced by activating the cardiac sympathetic afferent nerves through transient receptor potential vanilloid 1 (TRPV1) in cardiac afferent endings. Brainstem nucleus tractus solitarius (NTS) receives the sensory cardiac afferent inputs. Brain-derived neurotrophic factor (BDNF) is released within NTS from sensory neurons in an activity-dependent manner. Additionally, BDNF in NTS tonically regulates sympathetic activity. Therefore, we hypothesized that TRPV1-expressing cardiac afferent nerves contribute to cardiac hypertrophy in accompany with an increased BDNF expression in NTS. METHODS AND RESULTS: Abdominal aortic banding (AB) or sham operation was conducted in wild-type C57BL/6 J (WT-AB) and TRPV1 knockout mice (TRPV1 KO-AB). At 8 weeks post-operation, echocardiographic left ventricular wall thickness and heart weight/body weight ratio were significantly greater in WT-AB than WT-Sham mice, and these hypertrophic indexes were attenuated in TRPV1 KO-AB mice. Among the groups, left ventricular fractional shortening was not different. The protein levels of TRPV1 in heart and BDNF in NTS were significantly increased in WT-AB compared to WT-Sham mice, whereas BDNF expression in NTS was not increased by AB in TRPV1-KO mice. Chemical ablation of TRPV1-expressing cardiac afferents attenuated the AB-induced cardiac hypertrophy and increase in BDNF in NTS. Sympathetic activity analyzed using heart rate variability, and sympathoexcitatory responses to the stimulation of cardiac afferents were increased in WT-AB compared to WT-Sham mice. CONCLUSION: TRPV1-expressing cardiac afferent nerves may contribute to pressure overload-induced cardiac hypertrophy in accompany with the increased BDNF within NTS.

Low Body Mass Index without Malnutrition Is an Independent Risk Factor for Major Cardiovascular Events in Patients with Hemodialysis.

We retrospectively analyzed major cardiovascular events (MACE), a composite of cardiac death, nonfatal myocardial infarction, unplanned revascularization, heart failure leading to hospitalization, and stroke during a 3-year follow-up of patients with hemodialysis at the dialysis center of our general hospital that can treat comprehensive diseases. Moreover, we conducted an exploratory study that focuses on the risk factor for MACE in patients with hemodialysis.A total of 132 patients with hemodialysis at our dialysis center as of June 2017 were included in the study. Data on event incidence, including death and various clinical indicators, were collected in the electronic medical record for three years until June 2020. Between June 2017 and June 2020, of the 132 patients with hemodialysis, 31 patients experienced MACE (10 cardiovascular deaths, 3 nonfatal myocardial infarction, 11 unplanned revascularizations, 5 heart failure leading to hospitalization, and 2 stroke). The patients with MACE had a lower body mass index (BMI), longer duration of dialysis with more preexisting gastrointestinal (GI) bleeding, and took more aspirin compared to the MACE-free patients. Malnutrition markers (serum total protein, serum albumin, and serum total cholesterol) were similar in both groups. In a univariate analysis for MACE, the odds ratio was significantly higher for BMI < 18.5, duration of hemodialysis, and history of GI bleeding. Multivariable-adjusted odds ratios for MACE were significantly higher for BMI < 18.5.In conclusion, BMI < 18.5 without malnutrition may be an independent risk factor for MACE in patients with hemodialysis.

Serum High-Sensitivity C-Reactive Protein Levels and the Development of Atrial Fibrillation in a General Japanese Population　- The Hisayama Study.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia in the elderly, and causes complications such as cardioembolic stroke. Serum high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation, has been reported to be a risk factor for developing AF in Western countries. However, few community-based studies have examined this issue in general Asian populations.Methods and Results:A total of 2,510 community-dwelling Japanese participants aged ≥40 years without a history of AF were divided into 4 groups according to the sex-specific quartiles of serum hs-CRP concentrations (Q1, lowest and Q4, highest) and followed up for 24 years. The hazard ratios and their 95% confidence intervals for the development of AF were estimated using a Cox proportional hazards model. During the follow up, 234 subjects developed AF. The risk of AF increased significantly with elevating serum hs-CRP levels after adjustment for potential confounding factors (hazard ratio [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.26 [0.83-1.92]; Q3, 1.77 [1.18-2.66]; and Q4, 1.89 [1.24-2.86]; P for trend <0.001). CONCLUSIONS: The study findings suggest that elevated serum hs-CRP levels are an independent risk factor for the development of AF in a general Japanese population.

Olmesartan combined with renal denervation reduces blood pressure in association with sympatho-inhibitory and aldosterone-reducing effects in hypertensive mice with chronic kidney disease.

BACKGROUND: Augmented sympathetic nerve activity (SNA) and renin-angiotensin-aldosterone system (RAAS) activity are involved in the pathogenesis of hypertension (HT) accompanied by chronic kidney disease (CKD). Oxidative stress in the hypothalamus increases SNA in HT. Administration of an angiotensin ΙΙ receptor blocker (olmesartan; OLM) or renal denervation (RDN) exerts an antihypertensive effect in HT with CKD; however, the precise mechanisms of the combination therapy are not fully elucidated. In the present study, we examined whether combination therapy with OLM and RDN reduces both SNA by decreasing oxidative stress in the hypothalamus and RAAS activity in hypertensive mice with CKD. METHODS AND RESULTS: In 5/6-nephrectomized ICR-mice (Nx-mice) at 4-weeks after nephrectomy, systolic blood pressure (SBP) was significantly increased, accompanied by increased SNA and albuminuria compared with control-mice. Nx-mice were orally administered OLM, vehicle, or underwent RDN during OLM administration, and divided into Nx-OLM, Nx-VEH, and Nx-OLM/RDN groups, respectively. In Nx-OLM and Nx-OLM/RDN compared with Nx-VEH at 8-weeks after treatment, SBP was significantly decreased and both SNA and oxidative stress levels in the hypothalamus were significantly suppressed, without worsened creatinine clearance. In Nx-OLM and Nx-OLM/RDN compared with Nx-VEH, albuminuria was also suppressed, and the heart per body weight was decreased. In Nx-OLM/RDN, but not in Nx-OLM, the plasma aldosterone concentration was significantly decreased compared with Nx-VEH. CONCLUSION: These findings suggest that combination therapy with OLM/RDN has antihypertensive effects in association with suppressing SNA by reducing oxidative stress in the hypothalamus and the plasma aldosterone concentration in hypertensive mice with CKD.

Deletion of hypoxia-inducible factor-1α in myeloid lineage exaggerates angiotensin II-induced formation of abdominal aortic aneurysm.

Hypoxia-inducible factor (HIF)-1α is a transcription factor that regulates various genes responding to hypoxic conditions. We previously reported that myeloid-specific activation of HIF-1α had protective effects on hypertensive cardiovascular remodelling in mice. However the role of myeloid lineage HIF-1α in the development of abdominal aortic aneurysm (AAA) has not been determined. Myeloid-specific HIF-1α knockout (HIF-1KO) mice were created using a Cre-lox recombination system in the background of apolipoprotein E-deficient (ApoE-/-) mice. HIF-1KO and control mice were fed high-fat diet (HFD) and infused with angiotensin II (Ang II, 1800 ng/kg/min) by an osmotic mini pump for 4 weeks to induce AAA formation. Deletion of HIF-1α increased aortic external diameter (2.47±0.21 mm versus 1.80±0.28 mm in control, P=0.035). AAA formation rate (94.4% in HIF-1KO versus 81.8% in control) was not statistically significant. Elastic lamina degradation grade determined by Elastica van Gieson (EVG) staining was deteriorated in HIF-1KO mice (3.91±0.08 versus 3.25±0.31 in control, P=0.013). The number of infiltrated macrophages into the abdominal aorta was increased in HIF-1KO mice. Expression of tissue inhibitors of metalloproteinases (TIMPs) was suppressed in the aorta and peritoneal macrophages (PMs) from HIF-1KO mice compared with control mice. HIF-1α in myeloid lineage cells may have a protective role against AAA formation induced by Ang II and HFD in ApoE-/- mice.

Cardiac sympathetic afferent stimulation induces salt-sensitive sympathoexcitation through hypothalamic epithelial Na+ channel activation.

The cardiac sympathetic afferent (CSA), which plays an important role in heart-brain communication for sympathoexcitation, is stimulated in heart failure. Additionally, high salt intake leads to further sympathoexcitation due to activation of hypothalamic epithelial Na(+) channels (ENaCs) in heart failure. In the present study, we stimulated the CSA in adult male mice by epicardial application of capsaicin and using ethanol as a control to determine whether CSA stimulation led to activation of hypothalamic ENaCs, resulting in salt-induced sympathoexcitation. Three days after capsaicin treatment, an upregulation of hypothalamic α-ENaCs, without activation of mineralocorticoid receptors, was observed. We also examined expression levels of the known ENaC activator TNF-α. Hypothalamic TNF-α increased in capsaicin-treated mice, whereas intracerebroventricular infusion of the TNF-α blocker etanercept prevented capsaicin-induced upregulation of α-ENaCs. To examine brain arterial pressure (AP) sensitivity toward Na(+), we performed an intracerebroventricular infusion of high Na(+)-containing (0.2 M) artificial cerebrospinal fluid. AP and heart rate were significantly increased in capsaicin-treated mice compared with control mice. CSA stimulation also caused excitatory responses with high salt intake. Compared with a regular salt diet, the high-salt diet augmented AP, heart rate, and 24-h urinary norepinephrine excretion, which is an indirect marker of sympathetic activity with mineralocorticoid receptor activation, in capsaicin-treated mice but not in ethanol-treated mice. Treatment with etanercept or the ENaC blocker benzamil prevented these salt-induced excitatory responses. In summary, we show that CSA stimulation leads to an upregulation of hypothalamic α-ENaCs mediated via an increase in TNF-α and results in increased salt sensitivity.

Combining irbesartan and trichlormethiazide enhances blood pressure reduction via inhibition of sympathetic activity without adverse effects on metabolism in hypertensive rats with metabolic syndrome.

Sympathoexcitation and oxidative stress in the brain have pivotal roles in hypertension with metabolic syndrome (MetS). Here, we examined whether oral administration of irbesartan (IRB) and trichlormethiazide (TCM) decreases blood pressure (BP) via inhibiting sympathetic activity through anti-oxidant effects in the brain of spontaneously hypertensive rats (SHR-cp). IRB/TCM treatment decreased BP more profoundly than IRB monotherapy. Urinary norepinephrine excretion and oxidative stress in the brain were decreased in both IRB and IRB/TCM groups without any adverse effect on the metabolic profile. These findings suggest that IRB/TCM profoundly decreases BP in SHR-cp by inhibiting sympathetic activity via anti-oxidant effects in the brain.

Benefit of azilsartan on blood pressure elevation around rest-to-active phase in spontaneously hypertensive rats.

Abnormal elevation of blood pressure in early morning (rest-to-active phase) is suggested to cause cardiovascular events. We investigated whether azilsartan (AZL), a novel potent angiotensin receptor blocker, suppresses blood pressure elevation from the light-rest to dark-active phase in spontaneously hypertensive rats (SHRs). AZL has a sustained depressor effect around the rest-to-active phase in SHRs to a greater extent than candesartan (CAN), despite their similar depressor effects for over 24 h. AZL did not cause sympathoexcitation. These results suggest that AZL has a more sustained depressor effect than CAN around the rest-to-active phase in SHRs, and might have advantages for early morning hypertension.

Calorie restriction improves cognitive decline via up-regulation of brain-derived neurotrophic factor: tropomyosin-related kinase B in hippocampus ofobesity-induced hypertensive rats.

In metabolic syndrome (MetS), previous studies have suggested that cognitive decline is worsened. Among the factors associated with cognition, decreased brain-derived neurotrophic factor (BDNF) in the hippocampus causes cognitive decline. We previously reported that exercise training with calorie restriction yielded protection against cognitive decline via BDNF in the hippocampus of hypertensive rats. The aim of the present study was to determine whether or not calorie restriction results in protection against cognitive decline via BDNF and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of MetS model rats. We divided dietary-induced obesity-prone and hypertensive rats (OP), as metabolic syndrome model rats, into three groups, fed with a high fat diet (HF), treated with calorie restriction (CR) plus vehicle, and treated with CR and ANA-12 (a TrkB antagonist) (CR+A). After treatment for 28 days, body weight, insulin, fasting blood glucose, adiponectin, systolic blood pressure, and oxidative stress in the hippocampus were significantly lower, and BDNF expression in the hippocampus was significantly higher in CR and CR+A than in HF. Cognitive performance determined by the Morris water maze test was significantly higher in CR than in HF, whereas the benefit was attenuated in CR+A. In conclusion, calorie restriction protects against cognitive decline via up-regulation of BDNF/TrkB through an antioxidant effect in the hippocampus of dietary-induced obesity rats.

Japanese soybean paste miso lessens sympathovagal imbalance and attenuates brain sodium sensitivity in mice with pressure overload.

Miso is a traditional Japanese food that is made from fermented soybeans, and it can attenuate salt-induced hypertension in salt-sensitive hypertensive rats. We also recently demonstrated that regular miso intake inhibits salt-sensitive sympathoexcitation in mice with pressure overload (CPO). In this context, sympathoexcitation contributes to the pathogenesis of hypertension, including salt-sensitive hypertension. Therefore, we hypothesized that miso might be able to improve sympathovagal imbalance, thereby attenuating salt-induced hypertension. We first treated mice with an intraperitoneal (IP) injection of miso supernatant that was suspended in a 0.28 M sodium solution. Five hours after the miso injection, the mice's systolic blood pressure and heart rate had decreased, with a lower ratio of low frequency (LF) to high frequency (HF) power of heart rate variability. However, an IP injection of high-sodium saline solution (0.28 M sodium) alone had no effects on these parameters. To evaluate the effects of miso on sodium sensitivity in CPO-mice, we also performed aortic banding. At 4 weeks after the surgery, the mice received an IP injection of miso supernatant or high-sodium saline. The ratio of LF/HF increased after the high-sodium saline injection, although not after the miso injection, which indicated that miso inhibited the enhanced sodium sensitivity for sympathetic activity in CPO-mice. We also pre-treated CPO-mice with an intracerebroventricular infusion of miso supernatant to evaluate its effect on increased cerebrospinal fluid (CSF) sodium-induced hypertension. Diluted miso supernatant (in a 0.14 M sodium solution) attenuated the increased CSF sodium-induced hypertension, although pre-treatment with normal-sodium (0.14 M) saline failed to change the hypertension. These results suggest that miso acts on the brain to sway the sympathovagal balance towards a parasympathetic nerve dominant state, and to attenuate the brain sodium sensitivity for sympathoexcitation in CPO-mice.

Angiotensin II type 1 receptor expression in astrocytes is upregulated leading to increased mortality in mice with myocardial infarction-induced heart failure.

Enhanced central sympathetic outflow worsens left ventricular (LV) remodeling and prognosis in heart failure after myocardial infarction (MI). Previous studies suggested that activation of brain angiotensin II type 1 receptors (AT1R) in the brain stem leads to sympathoexcitation due to neuronal AT1R upregulation. Recent studies, however, revealed the importance of astrocytes for modulating neuronal activity, but whether changes in astrocytes influence central sympathetic outflow in heart failure is unknown. In the normal state, AT1R are only weakly expressed in astrocytes. We hypothesized that AT1R in astrocytes are upregulated in heart failure and modulate the activity of adjacent neurons, leading to enhanced sympathetic outflow. In the present study, by targeting deletion of astrocyte-specific AT1R, we investigated whether AT1R in astrocytes have a key role in enhancing central sympathetic outflow, and thereby influencing LV remodeling process and the prognosis of MI-induced heart failure. Using the Cre-LoxP system, we generated glial fibrillary acidic protein (GFAP)-specific AT1R knockout (GFAP/AT1RKO) mice. Urinary norepinephrine excretion for 24 h, as an indicator of sympathoexcitation, was significantly lower in GFAP/AT1RKO-MI mice than in control-MI mice. LV size and heart weight after MI were significantly smaller in GFAP/AT1RKO mice than in control mice. Prognosis was significantly improved in GFAP/AT1RKO-MI mice compared with control-MI mice. Our findings indicated that AT1R expression was upregulated in brain stem astrocytes in MI-induced heart failure, which worsened LV remodeling and prognosis via sympathoexcitation. Thus, in addition to neuronal AT1R, AT1R in astrocytes appear to have a key role in enhancing central sympathetic outflow in heart failure.

Novel dual endothelin receptor antagonist macitentan reverses severe pulmonary arterial hypertension in rats.

The efficacy of endothelin (ET) receptor antagonist bosentan in patients with severe pulmonary arterial hypertension (PAH) remains limited, partly because its higher doses for potential blockade of ET receptors have never been tested due to liver dysfunction. We hypothesized that rigorous blockade of ET receptors using the novel dual ET receptor antagonist macitentan would be effective in treating severe PAH without major side effects in a preclinical model appropriately representing the human disorder. In normal rats, 30 mg·kg·d of macitentan completely abolished big ET-1-induced increases in right ventricle (RV) systolic pressure. Adult male rats were injected with SU5416, a vascular endothelial growth factor blocker, and exposed to hypoxia for 3 weeks and then to normoxia for an additional 5 weeks (total 8 weeks). In intrapulmonary arterial rings isolated from rats with severe PAH, macitentan concentration dependently inhibited ET-1-induced contraction. Long-term treatment with macitentan (30 mg·kg·d, from week 3 to 8) reversed the high RV systolic pressure with preserved cardiac output. Development of RV hypertrophy, luminal occlusive lesions and medial wall thickening were also significantly improved without increasing serum levels of liver enzymes by macitentan. In conclusion, efficacious blockade of ET receptors with macitentan would reverse severe PAH without major adverse effects.

Corticosterone-activated mineralocorticoid receptor contributes to salt-induced sympathoexcitation in pressure overload mice.

Abstract We previously reported that pressure overload (PO) activates the hypothalamic mineralocorticoid receptor (MR) and angiotensin II type 1 receptor (AT1R). Moreover, salt intake further activates the hypothalamic MR and AT1R, resulting in salt-induced sympathoexcitation. However, the mechanism underlying this pathway activation in response to a high salt intake remains unknown. Although the role of aldosterone is extensively examined as a ligand for MR, corticosterone is able to bind to MR. Therefore, we hypothesized that corticosterone contributes to salt-induced sympathoexcitation in PO-mice. Four weeks after aortic banding to produce PO-mice, or a sham operation for controls, the mice were fed a high-salt diet for an additional 4 weeks. Compared to Sham-mice, the expression levels of hypothalamic MR, serum glucocorticoid-induced kinase 1 (a marker of MR activity) and AT1R increased in PO-mice. Salt intake further increased the expression levels of these proteins only in PO-mice with the increases in sympathetic activity evaluated on the basis of the excretion of 24-h urinary norepinephrine excretion. Bilateral adrenalectomy or the intraperitoneal infusion of metyrapone, a corticosterone synthase inhibitor, attenuated salt-induced sympathoexcitation via inhibition of the hypothalamic MR and AT1R activity. These adrenalectomy-induced alterations disappeared after corticosterone replacement therapy. We also found decreased expression levels of 11ß-hydroxysteroid dehydrogenase type 2, suggesting that corticosterone is apt to bind to MR. These results indicate that salt intake in PO-mice causes sympathoexcitation via, at least in part, corticosterone-induced MR and AT1R activation in the hypothalamus.

Miso (Japanese soybean paste) soup attenuates salt-induced sympathoexcitation and left ventricular dysfunction in mice with chronic pressure overload.

The hypothalamic mineralocorticoid receptor (MR)-angiotensin II type 1 receptor (AT1R) pathway is activated in mice with chronic pressure overload (CPO). When this activation is combined with high salt intake, it leads to sympathoexcitation, hypertension, and left ventricular (LV) dysfunction. Salt intake is thus an important factor that contributes to heart failure. Miso, a traditional Japanese food made from fermented soybeans, rice, wheat, or oats, can attenuate salt-induced hypertension in rats. However, its effects on CPO mice with salt-induced sympathoexcitation and LV dysfunction are unclear. Here, we investigated whether miso has protective effects in these mice. We also evaluated mechanisms associated with the hypothalamic MR-AT1R pathway. Aortic banding was used to produce CPO, and a sham operation was performed for controls. At 2 weeks after surgery, the mice were given water containing high NaCl levels (0.5%, 1.0%, and 1.5%) for 4 weeks. The high salt loading in CPO mice increased excretion of urinary norepinephrine (uNE), a marker of sympathetic activity, in an NaCl concentration-dependent manner; however, this was not observed in Sham mice. Subsequently, CPO mice were administered 1.0% NaCl water (CPO-H) or miso soup (1.0% NaCl equivalent, CPO-miso). The expression of hypothalamic MR, serum glucocorticoid-induced kinase-1 (SGK-1), and AT1R was higher in the CPO-H mice than in the Sham mice; however, the expression of these proteins was attenuated in the CPO-miso group. Although the CPO-miso mice had higher sodium intake, salt-induced sympathoexcitation was lower in these mice than in the CPO-H group. Our findings indicate that regular intake of miso soup attenuates salt-induced sympathoexcitation in CPO mice via inhibition of the hypothalamic MR-AT1R pathway.

[Effect of sympathetic nervous system on circadian rhythm of blood pressure].

There is evidence that the abnormal circadian rhythm of blood pressure (BP), such as absent of nocturnal BP fall and exaggerated morning BP surge, assessed by ambulatory BP monitoring is associated with cardiovascular events independent of BP levels in hypertensive patients. The activation of the sympathetic nervous system (SNS) is one of the most important pathophysiological mechanisms underlying abnormalities in circadian BP by affecting cardiac output, salt and volume balance in the kidney, and peripheral vascular resistance. In treating hypertension, especially accompanied by the abnormal circadian rhythm of BP, the effect of antihypertensive drug on SNS activity, as well as the timing of drug administration or the duration of the drug efficacy, should be considered.

The effects of renal denervation on blood pressure, cardiac hypertrophy, and sympathetic activity during the established phase of hypertension in spontaneously hypertensive rats.

This study aimed to investigate whether renal denervation (RDN) reduces blood pressure and attenuates cardiac hypertrophy with decreasing sympathetic activity in spontaneously hypertensive rats (SHRs), a model of essential hypertension, during the established phase of hypertension. We performed RDN or sham operation in 15-weeks-old SHRs. Thirty days after RDN, mean blood pressure measured by telemetry, heart weight, left ventricular wall thickness assessed by echocardiography, and urinary norepinephrine levels were significantly decreased in the RDN group compared to the Sham group. Furthermore, oxidative stress, as indicated by thiobarbituric acid reactive substances, in the rostral ventrolateral medulla, a pivotal region regulating basal sympathetic tone, was significantly decreased in the RDN group. In conclusion, RDN reduces blood pressure and attenuates cardiac hypertrophy with sympathoinhibition in the established phase of hypertension in SHRs. These findings highlight the sympathoinhibitory effect of RDN and suggest that RDN may be a potential therapy for hypertensive cardiac hypertrophy. Renal denervation reduces blood pressure and attenuates cardiac hypertrophy with sympathoinhibition in the established phase of hypertension in spontaneously hypertensive rats. This study highlights the sympathoinhibitory effect of renal denervation and suggests that renal denervation may be a potential therapy for hypertensive cardiac hypertrophy.

Gastrointestinal bleeding among 151 patients undergoing maintenance hemodialysis for end-stage renal failure: A 5-year follow-up study.

Gastrointestinal bleeding is one serious complication of patients undergoing hemodialysis with end-stage renal failure. The present study aimed to evaluate risks and clinical features of real-world clinical data on upper and lower gastrointestinal bleeding in patients undergoing hemodialysis during a 5-year longitudinal observation period. This study included 151 patients undergoing maintenance hemodialysis at Takagi Hospital between December 2017 and December 2022. Clinical data from December 2017 were recorded, and upper and lower gastrointestinal bleeding, mortality, prescribed medications, and bone fractures were examined during the five-year observation period. Of 151 patients, 32 (21.2%:4.2% per year) experienced bleeding, 24 had upper gastrointestinal bleeding, 7 had lower gastrointestinal bleeding, and one had an unknown origin of bleeding. Ulcers or erosions primarily cause upper gastrointestinal bleeding without Helicobacter pylori infection, whereas patients with H pylori eradication are more likely to experience bleeding caused by vascular lesions, often accompanied by underlying comorbidities. The prophylactic effects of proton pump inhibitors and histamine-2 receptor blockers were limited in hemodialysis patients, as 15 out of 24 patients with upper gastrointestinal bleeding (62.5%) were prescribed these medications. The mortality rate in patients with lower gastrointestinal bleeding (71.4%) was higher than that in those without bleeding (33.6%) (P < .05). All patients with lower gastrointestinal bleeding were prescribed nonsteroidal anti-inflammatory drugs and/or aspirin. In this study, endoscopic hemostasis was successfully achieved. The present study indicated that the incidence of gastrointestinal bleeding during hemodialysis was relatively high. Upper gastrointestinal bleeding may develop even with the prescription of proton pump inhibitors. Lower gastrointestinal bleeding was a complication in hemodialysis patients under serious pathological condition with nonsteroidal anti-inflammatory drugs and or aspirin.

Lower body bone fractures have high mortality rates and poor prognosis in the patients with hemodialysis.

INTRODUCTION: The objective of the current study was to investigate the association between lower body bone fractures occurring during maintenance hemodialysis and prognosis. METHODS: This study included 151 hemodialysis patients at the dialysis center of our hospital as of December 2017, and data were systematically gathered from medical records over a period of 5 years, concluding in December 2022. RESULTS: Fourteen patients, 3.0 per 100 person-years, in 151 hemodialysis patients suffered from lower body bone fractures. The ratio of males was significantly lower, and age was significantly higher in the lower body bone fracture group than in the no lower body bone fracture group. Duration of hemodialysis prior to entry into this study was significantly shorter in the lower body bone fracture group than in the no lower body bone fracture group. Serum albumin was significantly lower and alkaline phosphatase was significantly higher in the lower body bone fracture group than in the no lower body bone fracture group. Mortality rate was significantly higher in the lower body bone fracture group (85.7%) compared to no lower body bone fracture group (28.5%) (p = 0.01). Kaplan-Meier survival curves for mortality showed that lower body bone fracture group had poor prognosis compared to no lower body bone fracture group. Multivariable-adjusted odds ratio for mortality were significantly higher for cases with lower body bone fractures. CONCLUSION: Lower body bone fractures have high mortality rates and poor prognosis in the patients with hemodialysis.