Hypertension Research最新文献

The prevalence of hypertension in Japan remains high, owing to the high salt content of the typical Japanese diet. Dairy-based foods may reduce blood pressure and hypertension risk. However, dairy consumption is low in Japan, and the relationships between dairy intake and blood pressure or the mechanisms by which dairy products affect blood pressure are not fully understood. This cross-sectional study was conducted as part of the Iwaki Health Promotion Project in Aomori, Japan. A total of 1071 participants were included from those who underwent annual medical checkups in June 2015. Adjusted multivariate linear and logistic regression analyses were performed to analyze the relationships between dairy consumption and blood pressure or hypertension risk. Comprehensive blood biomarker measurements were also performed. Whole- and high-fat dairy consumption was found to have significant inverse associations with systolic blood pressure (SBP) for all participants (β = -0.0213, P = 0.044) and with SBP and systolic hypertension risk for non-users of antihypertensive medicines (β = -0.0306, P = 0.011; and OR = 0.9927, P = 0.016; respectively). Three blood biomarkers related to phosphorus metabolism (inorganic phosphorus, intact parathyroid hormone, and interleukin-6) were associated with both dairy consumption and SBP. Dairy consumption had a partial inverse association with SBP and hypertension risk in a Japanese population with high salt and low dairy consumption. Analysis of blood biomarkers suggested that phosphorus metabolism is involved in the associations between dairy consumption and blood pressure.

The hypertension patient population has doubled since 1990, affecting 1.3 billion globally and >75% live in low-and middle-income countries. Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB) are the most prescribed drugs (>160 million times in the US), but mortality increased >30% since 1990s globally. Clinical relevance of Myxomatous Mitral Valve Disease (MMVD) is directly linked to WHO group 2 pulmonary hypertension, with no disease specific therapies. Therefore, MMVD pet dogs with elevated systolic blood pressure treated with ACEI/ARB, were supplemented with oral ACE2 enzyme and Angiotensin1-7 (Ang1-7) bioencapsulated in plant cells. The oral ACE2/Ang1-7 was well tolerated by healthy and MMVD dogs with no adverse events and increased sACE2 activity by 670-755% with ARB (Telmisartan) than with ACEI (Enalapril) background therapy. In vitro rhACE2 activity was inhibited >90% by ACEIs enalapril/benazeprilat at higher doses but lisinopril inhibited at much lower doses. Membrane ACE2 activity evaluated in exosomes was 43-fold higher than the sACE2 and this was also inhibited 211% by ACEI, when compared to ARB. Background ACEI treatment reduced the Ang-II pool by 11-20-fold and proportionately decreased the abundance of Ang1-7 + Ang1-5 peptides. In contrast, ARB treatment increased Ang-II pool 11-20-fold and Ang1-7 + Ang1-5 by 160-260%. Systolic blood pressure was regulated by ARB better than ACEI, despite very high Ang-II levels. This first report on evaluation of metabolic pools in the RAS pathway identifies surprising interactions between ACEI/ARB/ACE2 and significant changes in key molecular dynamics. Affordable biologics developed in plant cells may offer potential new treatment options for hypertension.

The optimal blood pressure (BP) in patients with chronic kidney disease (CKD) remains uncertain. Therefore, this cohort study aimed to investigate the prognostic value of ambulatory blood pressure (ABP) in patients with CKD and to determine the optimal range for ABP. In total, 1051 hospitalized patients with CKD were enrolled. The prognosis of patients with CKD was evaluated in terms of all-cause death, cardiovascular death, cardiovascular events, and renal events. Our results showed that systolic blood pressure (SBP) had a higher predictive value than diastolic blood pressure in the multivariate-adjusted models. Additionally, nighttime SBP was found to be the best predictor of prognosis in patients with CKD. Furthermore, when dividing the nighttime SBP into quartiles (quartile 1: <110 mmHg, quartile 2: 110-124 mmHg, quartile 3:124-139 mmHg, and quartile 4: ≥139 mmHg). Nighttime SBP ≥ 124 mmHg had an impact on prognosis in patients with CKD, nighttime SBP 124-139 mmHg: total mortality (hazard ratio [HR], 3.017 [95% confidence interval (CI): 1.367-6.660]), cardiovascular death (HR, 2.570 [95% CI, 1.744-6.151]), all cardiovascular events (HR, 2.401 [95% CI, 1.288-4.475]), and 110-124 mmHg had an impact on the renal prognosis (HR, 1.975 [95% CI, 1.311-2.976]). Therefore, nighttime SBP is an independent risk factor for CKD and a significant predictor of prognosis in patients with CKD. Furthermore, the prognosis of patients with CKD improved when the nighttime SBP was maintained below 124 mmHg; however, maintaining it below 110 mmHg can further lower the incidence of renal disease.

Mechanical forces such as glomerular hyperfiltration are crucial in the pathogenesis and progression of diabetic kidney disease. Piezo2 is a mechanosensitive cation channel and plays a major role in various biological and pathophysiological phenomena. We previously reported Piezo2 expression in mouse and rat kidneys and its alteration by dehydration and hypertension. To elucidate the alteration of Piezo2 expression and its consequences in a mouse model of diabetic kidney disease, we used high salt-fed male KK-A^y mice, an accelerated genetic model of diabetic kidney disease. KK-A^y mice exhibited marked obesity, hyperglycemia, elevated blood pressure, higher creatinine clearance, and overt albuminuria. Histopathological analysis revealed glomerular hypertrophy, mesangial expansion, macrophage infiltration, tubular vacuolization, and interstitial fibrosis. The mRNA and protein expression analyses revealed (1) increased fibronectin protein expression in the glomerular areas, (2) upregulated Piezo2 expression in the glomerular mesangial cells and interstitial region, (3) increased Piezo2 and the fibronectin-coding gene Fn1 mRNA, and (4) a strong correlation of Piezo2 expression with that of Fn1 in the kidneys of diabetic kidney disease mice. Piezo2 upregulation and fibronectin accumulation were alleviated by an angiotensin II receptor blocker. In accordance with these in vivo results, in vitro study demonstrated that Piezo2 overexpression increased fibronectin production in HEK293T cells. In conclusion, we demonstrated that Piezo2 expression was upregulated in glomerular mesangial cells in a mouse model of diabetic kidney disease. Our results suggest that Piezo2 contributes to the progression of diabetic kidney disease by mediating glomerular fibronectin production, leading to glomerulosclerosis. Hyperfiltration is crucial in the pathogenesis of diabetic kidney disease. We showed that Piezo2 expression is upregulated in mesangial cells of diabetic kidney disease mice with glomerular fibronectin accumulation. Piezo2 overexpression increased fibronectin production in HEK293T cells. Piezo2 may contribute to diabetic kidney disease progression by mediating glomerular fibronectin production.

Long-term blood pressure (BP) variability (BPV) is associated with adverse prognosis in patients with heart failure. However, the clinical significance of very short-term (beat-to-beat) BPV is unclear. We collected data on nighttime pulse transit time-based continuous beat-to-beat BP measurement in patients with heart failure (n = 366, median age 72.0, male sex 53.3%). Coefficient of variation (CoV) of pulse transit time-based BP was considered as very short-term BPV. The primary outcome was a composite of heart failure hospitalization or cardiac death. Median values (25th and 75th percentiles) of systolic and diastolic BP CoV were 3.6% (2.8%, 4.5%) and 5.1% (3.8%, 6.5%), respectively. During a median follow-up period of 1084 days after BPV evaluation, 71 patients experienced the primary outcome. When the patients were divided into tertiles based on the systolic and diastolic BPV, the primary outcome occurred most frequently in the highest tertile of BPV. Multivariable Cox proportional hazard analysis revealed that systolic and diastolic BPV, as continuous variables, were independently associated with the primary outcome (hazard ratio 1.199 and 1.101, respectively). In conclusion, high nighttime very short-term BPV was associated with adverse prognosis in patients with heart failure.

Poor blood pressure control in treated patients with hypertension is an important topic in the field of hypertension, and an unmet need for new therapeutic drugs remains. Soluble guanylate cyclase (sGC), a key signal transduction enzyme responsible for vasodilation, has attracted increasing interest as a therapeutic target in various cardiovascular diseases. Two different sGC agonists, sGC stimulators and activators, can increase its enzymatic activity in reduced and oxidized/apo forms, respectively. With some sGC agonists being already in clinical use, drugs in this category are expected to become new therapeutic agents for various conditions, including hypertension. In this review, we summarize the current knowledge on the antihypertensive effects of sGC agonists in various preclinical studies involving animal models of spontaneous hypertension, salt-sensitive hypertension, nitric oxide-deficient hypertension, renin-angiotensin-aldosterone system-dependent hypertension, malignant hypertension, metabolic syndrome, renoprival hypertension, renovascular hypertension, drug-induced hypertension, pregnancy hypertension, and treatment-resistant hypertension. Our compilation provides a comprehensive rationale for advancing the clinical development of sGC agonists for the treatment of hypertension.

The effects of salt reduction and adequate nutrition intake among older adults with physical frailty remain controversial. Therefore, the present study investigated whether the association between daily salt intake and blood pressure among community-dwelling older adults, including the very old people, based on their physical frailty status. This cross-sectional study used data from the SONIC study, a cohort study on older adults, collected between 2010 and 2012. Daily salt intake was estimated from the brief self-administered diet history questionnaire. Participants were stratified by groups based on the use of antihypertensive medication and their physical frailty status. There were 1975 participants with an average age of 76.5 ± 6.5 years and 53.1% were female. No association was observed between daily salt intake and blood pressure among participants with physical frailty regardless of the use of antihypertensive medication. In contrast, an association was noted between daily salt intake and systolic blood pressure among the robust without antihypertensive medication group (β = 0.08, p = 0.038), and the odds ratios for systolic blood pressure ≥140 mmHg were significantly higher in the third and fourth quartiles of daily salt intake than in the first quartile (odds ratios = 1.78 and 1.71, respectively). The present results suggest that the physical frailty status needs to be considered when providing salt reduction guidance to older adults for blood pressure control, in order to prevent progression of frailty and maintain quality of life. Cross-sectional analysis of the association between salt intake and blood pressure in community-dwelling older adults in Japan (SONIC study): the results suggest that salt intake may not be related to blood pressure in older adults with physical frailty.