Triglyceride-Glucose Index Associated with Future Renal Function Decline in the General Population.

BACKGROUND: The triglyceride-glucose index (TyG index), calculated as the logarithmic product of fasting triglyceride and glucose concentrations, is recognized as a simple marker of insulin resistance. However, the association between the TyG index and future decline of renal function remains unclear in the general population. OBJECTIVE: To investigate whether the TyG index was associated with future decline of renal function in the general population who had not progressed to chronic kidney disease stage G2. DESIGN: Retrospective longitudinal observational cohort study. PARTICIPANTS: Individuals who received a population-based health checkup at JA Ehime Kouseiren Checkup Center from 2010 to 2019 (n = 134,007). Individuals without data of baseline fasting triglyceride or glucose levels, or baseline and follow-up data of estimated glomerular filtration rate (eGFR), or those with baseline eGFR < 60 mL/min/1.73 m2 were excluded. MAIN MEASURES: Future renal function decline, defined as a ≥ 25% decrease in eGFR from baseline. KEY RESULTS: Of 10,758 participants, 8,076 were classified into the low TyG index group (TyG index < 8.76, 1st to 3rd quartiles) and 2,682 into the high TyG index group (TyG index ≥ 8.76, 4th quartile). The mean follow-up period was 37.8 ± 23.6 months. The incidence rates of renal function decline were 0.31 and 0.69 per 100 person-years in the low and high TyG index groups, respectively. In multivariate Cox proportional hazard models, high TyG index was significantly associated with future renal function decline (hazard ratio 2.25, 95% CI 1.40-3.60). This association was consistent across subgroups stratified by age, sex, body mass index, baseline eGFR, and diagnosed hypertension, diabetes, or dyslipidemia. CONCLUSION: In the general population, high TyG index was associated with future renal function decline. The TyG index may be useful in identifying individuals at high risk for future renal function decline in the setting of health checkups.

Overview of the 87th Annual Scientific Meeting of the Japanese Circulation Society (JCS2023)　- New Challenge With Next Generation.

The 87thAnnual Meeting of the Japanese Circulation Society (JCS2023) was held in March 2023 in Fukuoka, Japan, marking the first in-person gathering after the COVID-19 pandemic. With the theme of "New Challenge With Next Generation" the conference emphasized the development of future cardiovascular leaders and technologies such as artificial intelligence (AI). Notable sessions included the Mikamo Lecture on heart failure and the Mashimo Lecture on AI in medicine. Various hands-on sessions and participatory events were well received, promoting learning and networking. Post-event surveys showed high satisfaction among participants, with positive feedback on face-to-face interactions and the overall experience. JCS2023, attended by 17,852 participants, concluded successfully, marking a significant milestone in post-pandemic meetings, and advancing cardiovascular medicine.

Nationwide Temporal Trends in Clinical Characteristics and Treatment of Dilated Cardiomyopathy From 2003 to 2013 in Japan　- A Report From Clinical Personal Records.

BACKGROUND: Little is known about nationwide temporal trends in the clinical characteristics and treatment of dilated cardiomyopathy (DCM) in Japan.Methods and Results: We collected data regarding demographics, echocardiography, and treatment of DCM between 2003 to 2013 from Clinical Personal Records, a national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Among the 40,794 DCM patients screened, 27,702 with left ventricular ejection fraction (LVEF) <50% and age ≥18 years were enrolled in this study and divided into 3 groups according to registration year: Group 1, 2003-2005 (10,006 patients); Group 2, 2006-2010 (11,252 patients); and Group 3, 2011-2013 (6,444 patients). Over time, there were decreases in age at registration (mean [±SD] 58.6±13.0 vs. 56.8±13.8 vs. 56.2±13.8 years; P<0.001) and LVEF (33.5±10.0% vs. 31.1±9.9% vs. 29.2± 9.7%; P<0.001), and an increase in patients with New York Heart Association Class III-IV (28.2% vs. 35.2% vs. 41.0%; P<0.001). The use of ß-blockers (59.1% vs. 79.3% vs. 87.8%; P<0.001) and mineralocorticoid receptor antagonists (30.6% vs. 35.8% vs. 39.7%; P<0.001) increased over time. In multivariate analysis, male sex, systolic blood pressure, chronic kidney disease, hemoglobin, and registration year were positively associated, whereas age and LVEF were negatively associated, with ß-blocker prescription. CONCLUSIONS: Although the clinical characteristics of DCM changed, the implementation of optimal medical therapy for DCM increased from 2003 to 2013 in Japan.

Evaluation of a Webinar for Pharmacists Learning Basic Clinical-Oncology during COVID-19 Pandemic in Japan.

It is essential for oncology pharmacists to update their knowledge, skills, and ethical attitudes. The Japanese Society of Pharmaceutical Oncology is an academic society for healthcare professionals involved in cancer treatment. It has conducted in-person seminars every year to cultivate the knowledge necessary for practicing advanced cancer medicine. Owing to the coronavirus disease (COVID-19) pandemic, the society was obligated to conduct a web-based seminar this year. A questionnaire survey was conducted before and after the webinar to explain how it works and to assess the learning attitudes of beginner and moderately skilled pharmacists in the field of oncology. Questionnaire surveys were conducted with the participants before and after watching the webinar. The questionnaires sought to determine participants' perspectives on the webinar and their knowledge of the seven modules. Of the 1756 webinar attendees, 1661 (94.6%) answered the pre-webinar survey and 1586 (90.3%) answered the post-webinar survey. Results indicate that the median post-webinar knowledge score was significantly higher than the median pre-webinar score (p < 0.001) in all modules. Principal component analysis of the degree of knowledge of seven modules revealed that the improved score group consisted of those from younger age groups, with less experience as pharmacists, non-society members, and those with less experience in past society seminars. Moreover, the web-based seminar provided a uniform learning effect throughout the country without distinguishing between urban and rural learners. The web-based educational program was an acceptable educational tool for Japanese oncology pharmacists.

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.

Evaluation of a web-based educational programme for pharmacists during the COVID-19 pandemic in Japan.

WHAT IS KNOWN AND OBJECTIVE: Continuing education is essential for pharmacists to acquire and maintain the knowledge, skills, and ethical attitudes necessary for clinical practice. However, with the emergence of COVID-19, the social circumstances and face-to-face learning environments have changed. The objectives of this study were to determine Japanese pharmacists' perception of a web-based educational programme in oncology, and assess changes in their understanding of pharmaceutical care in oncology before and after their participation in the webinar. METHODS: Questionnaire-based surveys were conducted for the participants of the web-based educational programme to determine their perspectives on the webinar, and their degree of comprehension of the five cancer types covered before and after watching the webinar. RESULTS AND DISCUSSION: Of the 1936 pharmacists taking the programme, all participated in the pre-webinar survey, and 1861 (96.1%) in the post-webinar survey. Compared with previous seminars that were held in the offline mode before the COVID-19 pandemic, 76.8% of respondents were significantly satisfied with the web-based educational programme. The median post-webinar comprehension scores in all modules were significantly higher than the median pre-webinar scores (p < 0.0001). A majority of the participants agreed that a web-based educational programme was satisfactory in acquiring knowledge. WHAT IS NEW AND CONCLUSION: This web-based educational programme was effective for Japanese pharmacists for postgraduate education in pharmaceutical care in oncology. To the best of our knowledge, our study is the first to report the effectiveness of a web-based educational programme for oncology pharmacists using a large population.

Undiagnosed Cardiac Sarcoidosis Causing Refractory Heart Failure After Acute Myocardial Infarction due to Thromboembolism.

A 61-year-old woman suffered chest pain and was admitted to a nearby hospital emergency department. She was diagnosed with acute myocardial infarction probably due to thromboembolism in the left anterior descending coronary artery and aspiration thrombectomy was performed. Afterwards, she developed refractory heart failure with severe global left ventricular dysfunction and was transferred to our hospital. An 18F-FDG-PET/CT scan revealed abnormal 18F-FDG uptake in non-infarcted regions of the left ventricle. Non-caseating granulomas were detected by biopsy from a skin eruption. She was diagnosed with cardiac sarcoidosis. In cases of refractory heart failure which cannot be explained only by myocardial infarction, evaluation of other undiagnosed cardiomyopathies is important for optimal management.

Post-acquisition hippocampal blockade of the NMDA receptor subunit GluN2A but not GluN2B sustains spatial reference memory retention.

While it has been shown that the blockade of N-methyl-d-aspartate type glutamate receptors (NMDARs) impairs memory acquisition, recent studies have reported that the post-acquisition administration of NMDAR antagonists suppresses spatial memory decay. These findings suggest that NMDARs are important not only for the acquisition of new memories but also for the decay of previously acquired memories. The present study investigated the contributions of specific NMDAR subunits to spatial memory decay using NVP-AAM077 (NVP), an NMDAR antagonist that preferentially binds to GluN2A subunits, and the selective GluN2B blocker Ro 25-6981 (Ro). Following Morris water maze training (four trials/day for four days), NVP and/or Ro were subchronically infused into the rat hippocampus for five days. Seven days after training, NVP-treated rats and NVP/Ro-treated rats explored the target area significantly more than the control and Ro-treated rats. These results demonstrate that post-acquisition treatment with NVP, but not Ro, suppresses the forgetting of previously acquired spatial memories. The NVP-treated rats more persistently explored the target area in the second test, which was conducted one day after the first, while the NVP/Ro-treated rats did not, which suggest that Ro treatment downregulates memory retention. In conclusion, the present results indicate that the NMDAR GluN2A and GluN2B subunits contribute to spatial memory deterioration and maintenance, respectively.

[Post-training N-methyl-D-aspartate receptor blockade facilitates retention of acquired spatial memory in rats].

We investigated the effect of a post-training chronic infusion of N-methyl-D-aspartate (NMDA) receptor blocker on retention of spatial reference memory in rats. In Experiment 1, we trained 4 groups of rats for 4 days (4 trials/ day) in the Morris water maze task. In a single probe trial after retention intervals of 1, 7, 14, and 28 days, the 1-day group showed more goal crossings than shown by the other 3 groups. In Experiment 2, a chronic infusion of the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (D-AP5) or a control vehicle into the lateral ventricle was initiated 1 day after the training session, and continued for 6 days. In the subsequent probe trial (7 days after training), the rats that had received the D-AP5 infusion showed significantly more goal crossings than the controls. These findings suggest that an NMDA receptor blockade following acquisition facilitates retention of spatial reference memory.

Renal denervation for hypertensive heart disease and atrial fibrillation.

Accumulating evidence supports the efficacy of renal denervation (RDN) as an antihypertensive treatment. Additionally, several RDN clinical studies, including meta-analyses, have suggested that RDN may potentially have beneficial effects on left ventricular hypertrophy, diastolic function, and new-onset/recurrence of atrial fibrillation (AF), although most studies were not randomized sham-controlled. In particular, the effects of RDN on left ventricular hypertrophy and AF recurrence appear to be relatively evident. Sympathetic activation plays a critical role in the development of hypertension, hypertensive heart disease, and AF. Notably, several studies suggest the cardioprotective effects of RDN even in the absence of significant blood pressure reduction, probably due to its sympathoinhibitory effects. It is imperative to establish the efficacy of RDN in patients with hypertensive heart disease and/or AF, focusing on parameters of sympathetic activity in the clinical setting, including randomized sham-controlled trials. Moreover, further basic research is essential to elucidate the therapeutic mechanisms of RDN beyond blood pressure lowering and the renal nerves-linked pathophysiologies of hypertensive heart disease and AF. This review outlines the effects of renal denervation on hypertensive heart disease, particularly on left ventricular hypertrophy and diastolic function, and on atrial fibrillation. The sympathoinhibitory effect of renal denervation, an important potential mechanism of its beneficial effects on heart disease, is also discussed.

Renal denervation: a key approach to hypertension and cardiovascular disease.

Sympathetic activation plays a critical role in the development of hypertension and cardiovascular disease, including heart failure and arrhythmias. Renal nerves contribute to the regulation of blood pressure and fluid volume through renal sympathetic efferent nerves, and to the modulation of sympathetic outflow through renal sensory afferent nerves. Previous studies including ours suggest that selective afferent renal denervation with preservation of efferent renal nerves can significantly decrease central sympathetic outflow in animal models of hypertension with renal damage. In Dahl salt-sensitive rats fed high salt diet from an early age, a model of hypertensive heart failure, this central sympathoinhibition by afferent renal denervation may attenuate the development of heart failure without significant blood pressure reduction. Accumulating clinical evidence supports the efficacy of renal denervation as an antihypertensive treatment. However, it remains important to clarify the appropriate indications and predictors of responders to renal denervation in the treatment of hypertension. Several clinical studies suggest beneficial effects of renal denervation in patients with heart disease, with or without hypertension, although most were not sham-controlled. In particular, some clinical studies have demonstrated that renal denervation reduces the incidence of atrial fibrillation or cardiovascular events even without a significant antihypertensive effect. It is essential to accumulate more insightful data in patients undergoing renal denervation, to establish the efficacy of renal denervation in patients with cardiovascular disease in the clinical setting, and to elucidate the therapeutic mechanisms of renal denervation and the renal nerves-linked pathophysiology of cardiovascular disease in basic research. This review outlines the effects of renal denervation on sympathetic activity and organ damage in animal models of hypertension and hypertensive heart failure, including our own data. Beyond the antihypertensive effects, the beneficial effects of renal denervation on cardiovascular disease are also discussed based on clinical studies. Several animal and clinical studies suggest the cardioprotective effects of renal denervation even in the absence of significant blood pressure reduction, probably due to its sympathoinhibitory effects.

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.

Esaxerenone: blood pressure reduction and cardiorenal protection without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Mineralocorticoid receptor (MR) is involved in the mechanisms of blood pressure elevation, organ fibrosis, and inflammation. MR antagonists have been used in patients with hypertension, heart failure, or chronic kidney disease. Esaxerenone, a recently approved MR blocker with a nonsteroidal structure, has demonstrated a strong blood pressure-lowering effect. However, blood pressure reduction may lead to sympathetic activation through the baroreflex. The effect of esaxerenone on the sympathetic nervous system remains unclear. We investigated the effect of esaxerenone on organ damage and the sympathetic nervous system in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP), a well-established model of essential hypertension with sympathoexcitation and organ damage. Three-week administration of esaxerenone or hydralazine successfully attenuated the blood pressure elevation. Both esaxerenone and hydralazine comparably suppressed left ventricular hypertrophy and urinary albumin excretion. However, renal fibrosis and glomerular sclerosis were suppressed by esaxerenone but not hydralazine. Furthermore, plasma norepinephrine level, a parameter of systemic sympathetic activity, was significantly increased by hydralazine but not by esaxerenone. Consistent with these findings, the activity of the control centers of sympathetic nervous system, the parvocellular region of the paraventricular nucleus in the hypothalamus and the rostral ventrolateral medulla, was enhanced by hydralazine but remained unaffected by esaxerenone. These results suggest that esaxerenone effectively lowers blood pressure without inducing reflex sympathetic nervous system activation. Moreover, the organ-protective effects of esaxerenone appear to be partially independent of its blood pressure-lowering effect. In conclusion, esaxerenone demonstrates a blood pressure-lowering effect without concurrent sympathetic activation and exerts organ-protective effects in salt-loaded SHRSP. Esaxerenone has antihypertensive and cardiorenal protective effects without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

Association of baseline electrocardiographic left ventricular hypertrophy with future renal function decline in the general population.

Electrocardiographic left ventricular hypertrophy (LVH) could predict adverse renal outcomes in patients with hypertension. This study aimed to investigate the association between electrocardiographic LVH and future decline in renal function in the general population using a dataset of population-based health checkups from 2010 to 2019 including 19,825 participants. Electrocardiographic LVH was defined according to the Minnesota code. Renal function decline was defined as a decrease of ≥ 25% in the estimated glomerular filtration rate from baseline to < 60 mL/min/1.73 m2. Electrocardiographic LVH was found in 1263 participants at the baseline visit. The mean follow-up period was 3.4 ± 1.9 years. The incidence rates of renal function decline were 0.30 and 0.78 per 100 person-years in the non-LVH group and LVH groups, respectively. Electrocardiographic LVH was associated with the risk for renal function decline in the adjusted analysis (hazard ratio 1.69, 95% confidence interval 1.14-2.50, P = 0.009). This association was comparable across subgroups stratified by age, sex, body mass index, diagnosed hypertension, systolic blood pressure, hemoglobin A1c, and urinary protein. This study underscores the usefulness of electrocardiographic LVH to detect high-risk individuals for renal function decline in the setting of health checkups in the general population.

2023 update and perspectives.

Total 276 manuscripts were published in Hypertension Research in 2022. Here our editorial members picked up the excellent papers, summarized the current topics from the published papers and discussed future perspectives in the sixteen fields. We hope you enjoy our special feature, 2023 update and perspectives in Hypertension Research.

Emerging topics on basic research in hypertension: interorgan communication and the need for interresearcher collaboration.

The pathogenesis of hypertension is multifactorial and highly complex. Basic research plays critical roles in elucidating the complex pathogenesis of hypertension and developing its treatment. This review covers recent topics in basic research related to hypertension in the following six parts: brain/autonomic nervous system, kidney, vascular system, potential treatments, extracellular vesicles, and gut microbiota. The brain receives afferent nerve inputs from peripheral organs, including the heart, kidneys, and adipose tissue, and humoral inputs from circulating factors such as proinflammatory cytokines and leptin, which are involved in the regulation of central sympathetic outflow. In the kidneys, changes in Wnt/ß-catenin signaling have been reported in several hypertensive models. New findings on the renin-angiotensin-aldosterone system in the kidneys have also been reported. Sirtuin 6, which participates in various cellular functions, including DNA repair, has been shown to have protective effects on the vascular system. Skin water conservation, mediated by skin vasoconstriction and the accumulation of osmolytes such as sodium, has been found to contribute to hypertension. Studies of rivaroxaban and sodium-glucose cotransporter-2 inhibitors as drug repositioning candidates have been performed. Extracellular vesicles have been shown to be involved in novel diagnostic approaches and treatments for hypertension as well as other diseases. In gut microbiota studies, interactions between microbiota and antihypertensive drugs and potential pathophysiology linking microbiota and COVID-19 have been reported. It can be seen that inter-organ communication has received particular attention from these recent research topics. To truly understand the pathogenesis of hypertension and to develop treatments for conquering hypertension, interresearcher communication and collaboration should be further facilitated. This mini-review focuses on recent topics on basic research in hypertension from the several points of view. The recent topics indicate that inter-organ communication has received particular attention. Interresearcher communication and collaboration should also be further facilitated to truly understand the complex pathogenesis of hypertension and to develop the treatments.

Contribution of afferent renal nerve signals to acute and chronic blood pressure regulation in stroke-prone spontaneously hypertensive rats.

The activation of sympathetic nervous system plays a critical role in the development of hypertension. The input from afferent renal nerves may affect central sympathetic outflow; however, its contribution to the development of hypertension remains unclear. We investigated the role of afferent renal nerves in acute and chronic blood pressure regulation using normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Acute chemical stimulation of afferent renal nerves elicited larger increases in blood pressure and renal sympathetic nerve activity in young 9-week-old SHRSP compared to WKY. Selective afferent renal denervation (ARDN) and conventional total renal denervation (TRDN) ablating both afferent and efferent nerves in young SHRSP revealed that only TRDN, but not ARDN, chronically attenuated blood pressure elevation. ARDN did not affect plasma renin activity or plasma angiotensin II levels, whereas TRDN decreased both. Neither TRDN nor ARDN affected central sympathetic outflow and systemic sympathetic activity determined by neuronal activity in the parvocellular region of hypothalamic paraventricular nucleus and rostral ventrolateral medulla and by plasma and urinary norepinephrine levels, respectively. Renal injury was not apparent in young SHRSP compared with WKY, suggesting that renal afferent input might not be activated in young SHRSP. In conclusion, the chronic input from afferent renal nerves does not contribute to the development of hypertension in SHRSP despite the increased blood pressure response to the acute stimulation of afferent renal nerves. Efferent renal nerves may be involved in the development of hypertension via activation of the renin-angiotensin system in SHRSP.

A higher resting heart rate is associated with cardiovascular event risk in patients with type 2 diabetes mellitus without known cardiovascular disease.

A higher resting heart rate (RHR) is associated with an increased risk of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The aim of this study was to investigate the association between RHR and cardiovascular events in T2DM patients with diabetic retinopathy and without known cardiovascular disease. We analyzed the association between RHR and cardiovascular events, including coronary, cerebral, renal and vascular events or cardiovascular death in T2DM patients with retinopathy and hyperlipidemia without prior cardiovascular events who were enrolled in the EMPATHY study. Data from 4746 patients were analyzed. The median RHR was 76 bpm. Patients were divided into four groups based on their baseline RHR ( < 60, 60-69, 70-79, and ≥80 bpm). Patients with a higher RHR were more likely to be younger and had a higher body mass index, blood pressure value, HbA1c value, and estimated glomerular filtration rate and a lower B-type natriuretic peptide value; they also had a higher proportion of current smoking status, neuropathy, and nephropathy. After adjusting for confounders, including the aforementioned risk factors, a RHR of 70-79 bpm and a RHR ≥ 80 bpm were significantly associated with cardiovascular events (hazard ratio 1.50, 95% CI 1.03-2.20; and hazard ratio 1.62, 95% CI 1.11-2.36; respectively) compared to a RHR of 60-69 bpm. The analysis using restricted cubic splines indicated that the cardiovascular risk seemed to be similarly high when the RHR range was ≥70 bpm. In conclusion, in T2DM patients with diabetic retinopathy and without known cardiovascular disease, a high RHR, particularly ≥70 bpm, was associated with the risk of cardiovascular events compared to a RHR of 60-69 bpm. High resting heart rate (RHR), particularly ≥70 bpm, was associated with the risk of cardiovascular events compared to RHR 60-69 bpm in patients with type 2 diabetes mellitus (T2DM), diabetic retinopathy, and hyperlipidemia, but without known cardiovascular disease.

Interstitial-fluid shear stresses induced by vertically oscillating head motion lower blood pressure in hypertensive rats and humans.

The mechanisms by which physical exercise benefits brain functions are not fully understood. Here, we show that vertically oscillating head motions mimicking mechanical accelerations experienced during fast walking, light jogging or treadmill running at a moderate velocity reduce the blood pressure of rats and human adults with hypertension. In hypertensive rats, shear stresses of less than 1 Pa resulting from interstitial-fluid flow induced by such passive head motions reduced the expression of the angiotensin II type-1 receptor in astrocytes in the rostral ventrolateral medulla, and the resulting antihypertensive effects were abrogated by hydrogel introduction that inhibited interstitial-fluid movement in the medulla. Our findings suggest that oscillatory mechanical interventions could be used to elicit antihypertensive effects.

Reduction of nitric oxide-mediated γ-amino butyric acid release in rostral ventrolateral medulla is involved in superoxide-induced sympathoexcitation of hypertensive rats.

BACKGROUND: The rostral ventrolateral medulla (RVLM) in the brainstem is responsible for regulation of the sympathetic nervous system. In the RVLM, nitric oxide (NO)-mediated γ-amino butyric acid (GABA) is a major sympathoinhibitory amino acid neurotransmitter and superoxide is a major sympathoexcitatory factor. In this study, we investigated whether or not NO-mediated GABA release is involved in superoxide-induced sympathoexcitation in the RVLM of hypertensive rats. METHODS AND RESULTS: For our model hypertensive rats with sympathoexcitation, we used stroke-prone spontaneously hypertensive rats (SHRSP). GABA levels in the RVLM were measured by in vivo microdialysis. Microinjection of tempol, a superoxide scavenger, into the RVLM decreased arterial pressure (AP), heart rate (HR), and renal sympathetic nerve activity (RSNA) with an increase in GABA release in the RVLM. Microinjection of N(G)-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, into the RVLM increased AP, HR, and RSNA with a decrease in GABA release in the RVLM. Prior microinjection of L-NMMA into the RVLM attenuated the tempol-induced changes in AP, HR, RSNA, and GABA release in the RVLM. Microinjection of bicuculline, a GABA receptor blocker, into the RVLM attenuated the tempol- and L-NMMA-induced changes in AP, HR, and RSNA. CONCLUSIONS: The findings suggest that reduction of NO-mediated GABA release in the RVLM is partly involved in superoxide-induced sympathoexcitation of SHRSP.