Hypertension Research最新文献

{"title":"A mouse model of hypertension induced by sucrose.","authors":"Yuki Nakayama, Hirotoshi Utsunomiya, Kunie Eguchi, Katherine J Elliott, Tomoki Hashimoto, Patrick Osei-Owusu, Satoru Eguchi","doi":"10.1038/s41440-025-02278-w","DOIUrl":"https://doi.org/10.1038/s41440-025-02278-w","url":null,"abstract":"","PeriodicalId":13029,"journal":{"name":"Hypertension Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Habibi et al. on 'Long-term blood pressure dysregulation after preeclampsia': toward integrated vascular profiling.","authors":"Maya Jälmby, Camilla Edvinsson, Despoina Lykou, Grigorios Karampas, Lena Erlandsson, Stefan R Hansson, Federica Piani","doi":"10.1038/s41440-025-02269-x","DOIUrl":"https://doi.org/10.1038/s41440-025-02269-x","url":null,"abstract":"","PeriodicalId":13029,"journal":{"name":"Hypertension Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of plasma BNP and NT-proBNP levels, and NT-proBNP/BNP ratio in patients with chronic kidney disease.","authors":"Hideki Fujii, Shunsuke Goto","doi":"10.1038/s41440-025-02272-2","DOIUrl":"https://doi.org/10.1038/s41440-025-02272-2","url":null,"abstract":"<p><p>Both B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are clinically used for diagnosing and monitoring heart failure. However, their levels are influenced by several factors, and their impacts on chronic kidney disease (CKD) patients remain unclear. This study included 1036 patients who visited the Nephrology division at our hospital between 2014 and 2015. Plasma BNP, NT-proBNP levels and the BNP/NT-proBNP ratio were measured at each CKD stage, and their correlation with clinical factors were analyzed. This study included 1037 patients with stage 1 to stage 5D CKD (CKD 1-2, n = 114; CKD 3, n = 256; CKD 4, n = 266; CKD 5, n = 298; CKD 5D, n = 102). Levels of plasma BNP and NT-proBNP levels and the NT-proBNP/BNP ratio increased, and the correlation between BNP and NT-proBNP levels weakened with declining kidney function. Although various clinical factors were found to be significantly correlated with these parameters, multivariate analysis showed that male gender and hemoglobin, phosphate, and parathyroid hormone levels were significantly correlated with both plasma BNP and NT-proBNP levels. Notably, a higher NT-proBNP/BNP ratio was significantly associated with increased cardiovascular events in patients with CKD stages 4 and 5. As plasma BNP and NT-proBNP levels are influenced by various factors in patients with CKD, careful interpretation of these parameters is essential. In patients with advanced-stage CKD, the NT-proBNP/BNP ratio may be a useful predictor of CVD development.</p>","PeriodicalId":13029,"journal":{"name":"Hypertension Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolated diastolic hypertension and incident cardio-renal-metabolic multimorbidity in the Tehran Lipid and Glucose Study: comparison of ACC/AHA and ESC/NICE guideline definitions.","authors":"Soroush Masrouri, Amirhossein Hasanpour, Danial Molavizadeh, Navid Ebrahimi, Fereidoun Azizi, Farzad Hadaegh","doi":"10.1038/s41440-025-02267-z","DOIUrl":"https://doi.org/10.1038/s41440-025-02267-z","url":null,"abstract":"<p><p>Hypertension is defined as ≥130/80 mm Hg by ACC/AHA 2017, and ≥140/90 mm Hg by the ESC 2018 and NICE 2019. We examined the association between isolated diastolic hypertension (IDH, by both thresholds) and cardio-renal-metabolic (CRM) multimorbidity. From 1999 to 2018, we followed 7377 (mean age: 37.7 years) and 6717 (36.8 years) Tehran Lipid and Glucose Study (TLGS) participants, initially free of cardiovascular disease (CVD), type 2 diabetes (T2DM), and chronic kidney disease, with systolic blood pressure (SBP) <140 and <130 mm Hg based on ESC/NICE and ACC/AHA criteria, respectively. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CRM multimorbidity (coexistence of ≥2 of CVD, kidney function decline [KFD], and T2DM). IDH was identified in 28.2% of participants using ACC/AHA criteria and 5.9% using ESC/NICE criteria. Over a median 15.3-year follow-up (IQR: 12.1-16.6), 182 CRM multimorbidity events occurred per ACC/AHA IDH criteria and 241 per ESC/NICE criteria. In the fully adjusted model, IDH by ESC/NICE criteria was not significantly associated with CRM multimorbidity (HR: 1.45 [95% CI: 0.98-2.15]), while stage 2 IDH by ACC/AHA criteria showed a significant association (2.15 [1.21-3.82]). Similar associations of IDH with incident CRM multimorbidity were observed across age groups, sex, current smoking, obesity, dyslipidemia, and prediabetes. IDH was associated with increased risks of T2DM, CVD, and KFD as individual outcomes. In conclusion, stage 2 IDH per ACC/AHA criteria is linked to a higher risk of incident CRM multimorbidity, independent of SBP levels.</p>","PeriodicalId":13029,"journal":{"name":"Hypertension Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of esaxerenone in hypertensive patients with chronic kidney disease, with or without type 2 diabetes mellitus: a pooled analysis of five clinical studies.","authors":"Haruhito A Uchida, Jun Wada, Hirohiko Motoki, Koichiro Kuwahara, Kazuomi Kario, Tomohiro Katsuya, Tatsuo Shimosawa, Kenichi Tsujita, Shoko Suzuki, Tomohiro Suedomi, Takashi Taguchi","doi":"10.1038/s41440-025-02259-z","DOIUrl":"https://doi.org/10.1038/s41440-025-02259-z","url":null,"abstract":"<p><p>Effective management of blood pressure (BP) and albuminuria are crucial for suppressing chronic kidney disease (CKD) progression and cardiovascular risks in hypertension. This pooled analysis evaluated the antihypertensive effects, organ-protective effects, and safety of esaxerenone in hypertensive patients with CKD by integrating five clinical studies of esaxerenone. Patients were divided based on type 2 diabetes mellitus (T2DM) status (with or without T2DM) and creatinine-based estimated glomerular filtration rate (eGFR_creat) (30 to <60 and ≥60 mL/min/1.73 m²). Significant changes in morning home BP from baseline at Week 12 were observed in the overall population (mean change -12.8/ - 5.4 mmHg), T2DM subgroups ( - 12.2/ - 4.5 and -14.5/ - 7.8 mmHg), and eGFR_creat subgroups ( - 12.5/ - 4.7 and -14.0/ - 6.9 mmHg) (all P < 0.001). Bedtime home and office BP showed similar tendencies. Urine albumin-to-creatinine ratio significantly improved from baseline at Week 12 in the overall population (mean change: -55.2%), T2DM subgroups ( - 56.5% and -52.0%), and eGFR_creat subgroups ( - 54.6% and -55.4%) (all P < 0.001). N-terminal pro-B-type natriuretic peptide levels significantly decreased in the overall population (percent change: -14.1%) and subgroup without T2DM ( - 25.3%). The incidence of serum potassium ≥5.5 mEq/L was lower in the subgroup with T2DM vs without T2DM (3.1% and 11.3%), potentially related to the use of sodium-glucose cotransporter 2 inhibitors. These findings highlight the sustained BP-lowering effect of esaxerenone throughout the day in hypertensive patients with CKD, irrespective of T2DM status, and its significant reduction in albuminuria. The data support the safety and efficacy of esaxerenone in this patient population, underscoring its potential as a valuable therapeutic option. This study showed that esaxerenone significantly lowered morning home, bedtime home, and office BP and UACR in hypertensive patients with CKD, regardless of T2DM status and kidney function (eGFR), and without any novel safety concerns. These highlight the efficacy, organ-protective effects, and safety of esaxerenone in hypertensive patients with CKD.</p>","PeriodicalId":13029,"journal":{"name":"Hypertension Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary cortisol-to-cortisone ratio levels modify the association between diabetes and hypertension: a cross-sectional study of 6931 older adults.","authors":"Chisato Shimanoe, Akiko Matsumoto, Yuichiro Nishida, Takuma Furukawa, Rintaro Sogawa, Mikako Horita, Hinako Nanri, Yasuki Higaki, Keitaro Tanaka, Megumi Hara","doi":"10.1038/s41440-025-02271-3","DOIUrl":"https://doi.org/10.1038/s41440-025-02271-3","url":null,"abstract":"<p><p>The incidence of hypertension and Type 2 diabetes mellitus (T2DM) is increasing, and their coexistence significantly increases the risk of cardiovascular diseases, stroke, nephropathy, retinopathy, and mortality. Mineralocorticoid receptor activity, primarily regulated by aldosterone, can be beneficially modulated by mineralocorticoid receptor antagonists, especially in patients with mineralocorticoid receptor-associated hypertension, which often occurs with obesity and T2DM. Thus, markers of mineralocorticoid receptor activation, such as 11β-hydroxysteroid dehydrogenase, may help identify patients who may not benefit from standard hypertension treatments. This study investigated the effects of the cortisol-to-cortisone ratio, a marker of 11β-hydroxysteroid dehydrogenase activity, on the relationship between T2DM and hypertension. Using a cross-sectional design, 6931 individuals aged 45-74 years from the Japan Multi-Institutional Collaborative Cohort Study were analyzed. Cortisol and cortisone levels in spot urine samples were measured using liquid chromatography-mass spectrometry. Hypertension (N = 3141) was observed among those who were older; male; current smokers; current drinkers; had T2DM, hyperlipidemia, high BMI; and low perceived stress, physical activity, and eGFR. Multiple logistic regression analysis was performed, and T2DM was associated with hypertension (odds ratio, 1.37; 95% CI, 1.14-1.66). This association varied with cortisol-to-cortisone ratio level and was more evident in participants with a higher odds ratio (2.01; 95% CI, 1.39-2.91; P_interaction = 0.040). These epidemiologic findings suggest that mineralocorticoid receptor activity and 11β-hydroxysteroid dehydrogenase regulation may play a role in hypertension among patients with T2DM, highlighting the potential for targeted treatments based on the cortisol-to-cortisone ratio.</p>","PeriodicalId":13029,"journal":{"name":"Hypertension Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between urinary sodium-to-potassium ratio and BNP in a general population without antihypertensive treatment and cardiovascular diseases: the Ohasama study.","authors":"Tomoko Muroya, Michihiro Satoh, Hirohito Metoki, Shingo Nakayama, Takuo Hirose, Takahisa Murakami, Yukako Tatsumi, Ryusuke Inoue, Megumi Tsubota-Utsugi, Azusa Hara, Mana Kogure, Naoki Nakaya, Kei Asayama, Kyoko Nomura, Masahiro Kikuya, Atsushi Hozawa, Takayoshi Ohkubo","doi":"10.1038/s41440-025-02266-0","DOIUrl":"https://doi.org/10.1038/s41440-025-02266-0","url":null,"abstract":"<p><p>The urinary sodium-to-potassium (Na/K) ratio is associated with blood pressure (BP) and cardiovascular risk. We examined the association between the urinary Na/K ratio and brain natriuretic peptide (BNP), a biomarker indicative of cardiac stress levels within the general population. This cross-sectional study included 436 participants (mean age: 65.4 ± 6.9 years; 73.2% women) without antihypertensive medications or cardiovascular diseases (including atrial fibrillation) from the Ohasama Study. The urinary Na/K ratio was calculated using casual daytime spot urine samples. Analyses of covariance and multiple linear and Poisson regression models were conducted. The median BNP value was 18.6 pg/mL (interquartile range: 11.4-31.2 pg/mL). Participants in the first (≤2.19), second (2.19-3.27), and third (≥3.28) tertiles of the urinary Na/K ratio had adjusted mean natural log-transformed (ln)BNP of 2.74, 2.88, and 3.06 (converted BNP values: 15.50, 17.81, and 21.37 pg/mL), respectively, after adjusting for covariates including estimated glomerular filtration rate, home systolic BP, and Sokolow-Lyon voltage (P for trend = 0.0005). The adjusted prevalence ratios (95% confidence intervals) for BNP ≥35 pg/mL were 1.27 (0.76-2.14) and 2.24 (1.35-3.72) in the second and third tertiles, respectively, compared with the lowest tertile. The highest standardized regression coefficient for lnBNP was observed for the urinary Na/K ratio ( | 0.24 | ), surpassing estimated 24-h urinary sodium ( | 0.16 | ) or potassium ( | 0.09 | ) excretion. In conclusion, urinary Na/K ratio was associated with elevated BNP levels in individuals without antihypertensive treatment and cardiovascular disease history. This urinary marker may be valuable for early prevention of organ damage and cardiac burden.</p>","PeriodicalId":13029,"journal":{"name":"Hypertension Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating blood pressure targets in chronic kidney disease: a systematic review and meta-analysis.","authors":"Kazuhiro Tada, Akira Fujiwara, Naoki Sugano, Kaori Hayashi, Atsushi Sakima, Yoichi Takami, Kosuke Masutani, Hisatomi Arima, Shuji Arima, Naoki Nakagawa","doi":"10.1038/s41440-025-02262-4","DOIUrl":"10.1038/s41440-025-02262-4","url":null,"abstract":"<p><p>Many studies have investigated optimal blood pressure (BP) targets in patients with chronic kidney disease (CKD); however, no consensus has been reached. We therefore conducted a systematic review and meta-analysis, including the latest randomized controlled trials (RCTs). We searched MEDLINE, the Cochrane Library, and Ichushi Web for publications up to 13 June 2024, supplemented by hand searches. We included RCTs comparing the benefits and risks of more intensive (target BP: <130/80 mmHg) versus less intensive BP control (target BP: 130-149/80-89 mmHg or usual care) in patients with CKD aged ≥18 years, regardless of diabetes status. Primary outcomes were all-cause mortality and cardiovascular events. Secondary outcomes included renal events, including 50% reduction in estimated glomerular filtration rate (eGFR)/GFR, and end-stage kidney disease (ESKD). We calculated the risk ratio (RR) and variance, and obtained summary estimates of the effects with 95% confidence intervals (CIs) using a random-effects model with inverse variance weighting. Our meta-analysis included nine RCTs. More intensive BP control tended to reduce all-cause mortality (RR = 0.81; 95% CI 0.65-1.00; p = 0.051) and cardiovascular events (RR = 0.89; 95% CI 0.77-1.03; p = 0.13), but the differences were not significant. More intensive BP control did not increase the risk of serious renal events, including 50% reduction in eGFR/GFR (RR = 0.95; 95% CI 0.74-1.22; p = 0.69) or progression to ESKD (RR = 0.92; 95% CI 0.75-1.14; p = 0.45). These findings suggest that intensive BP control targeting <130/80 mmHg may reduce the risk of all-cause mortality and cardiovascular events in patients with CKD, without increasing the risk of serious renal events. This meta-analysis of nine RCTs in patients with CKD found that more intensive BP control tended to reduce all-cause mortality and CVD events compared with less intensive control, without increasing serious kidney events, including 50% eGFR/GFR reduction, or ESKD.</p>","PeriodicalId":13029,"journal":{"name":"Hypertension Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic impact of the timing of antihypertensive medication initiation for hypertension detected at health screening on primary prevention of adverse cardiovascular events: Age-stratified real-world data analysis.","authors":"Hiromasa Ito, Tomohisa Seki, Yoshimasa Kawazoe, Toru Takiguchi, Yu Akagi, Kazumi Kubota, Kana Miyake, Masafumi Okada, Kazuhiko Ohe","doi":"10.1038/s41440-025-02249-1","DOIUrl":"10.1038/s41440-025-02249-1","url":null,"abstract":"<p><p>The association between age and timing of antihypertensive treatment initiation and its effect on outcomes of patients with hypertension remain unclear. We investigated the impact of the time to antihypertensive therapy initiation for cardiovascular event primary prevention in an age-stratified analysis using data from a nationwide health claims database. This observational cohort study analyzed claim and health examination data recorded between January 1, 2005, and April 30, 2021, in the Japan Medical Data Center database. Patients with hypertension treated with antihypertensive agents were grouped by time (years) to therapy initiation: <1 (reference group), 1-2, and ≥2. The primary outcome was a composite outcome encompassing cardiovascular death, acute coronary syndrome, heart failure, and cerebrovascular disease. The secondary outcome was all-cause mortality. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals adjusted for the time to treatment (TTI) group, age, male sex, systolic blood pressure, smoking status, dyslipidemia, diabetes, and visceral obesity. Among 520,669 participants, TTI ≥ 1 year conferred significantly higher hazard ratios for primary outcomes than TTI < 1 year in individuals aged ≥40 years. Hazard ratios (95% confidence intervals) for the primary outcome with TTI of 1-2 and >2 years were 1.215 (1.073-1.375) and 1.296 (1.163-1.444) in those aged 40-49 years and 1.268 (1.144-1.406) and 1.341 (1.224-1.468) in those aged 50-59 years, respectively. TTI ≥ 2 years was an independent prognostic factor for the secondary outcome of all-cause mortality in those aged ≥40 years.</p>","PeriodicalId":13029,"journal":{"name":"Hypertension Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidized LDL enhances Gq signaling and aldosterone production by angiotensin II via the AT1-LOX-1 receptor complex in adrenal cells.","authors":"Jittoku Ihara, Yibin Huang, Yoichi Takami, Yu Guo, Toshimasa Takahashi, Akemi Kakino, Yoichi Nozato, Cheng Wang, Ziwei Wang, Weidong Liu, Nanxiang Yin, Ryoichi Ohara, Akitoshi Hara, Hikari Takeshita, Hiromi Rakugi, Tatsuya Sawamura, Koichi Yamamoto","doi":"10.1038/s41440-025-02261-5","DOIUrl":"https://doi.org/10.1038/s41440-025-02261-5","url":null,"abstract":"<p><p>We previously reported that oxidized low-density lipoprotein (oxLDL) activates the angiotensin II (AII) type 1 receptor (AT1) through the lectin-like oxLDL receptor (LOX-1)-AT1 complex. While oxLDL alone does not activate G protein αq (Gq), its simultaneous binding with AII alters AT1 structure, enhancing Gq activation. We investigated this interaction's effect on aldosterone production in adrenal glands. Human adrenal cells (H295R) were treated with vehicle, oxLDL, AII, or a combination of oxLDL and AII. Gq signaling was assessed using inositol monophosphate (IP1) assays, Ca influx using Fura2, and aldosterone synthesis gene expression using qRT-PCR. Wild-type (WT) and LOX-1 knockout (KO) mice were fed a normal diet (ND) or high-fat diet (HFD) in vivo to elevate oxLDL levels, followed by subcutaneous AII or saline infusion for 4 weeks (long-term) or 3 days (short-term). In H295R cells, oxLDL alone did not induce IP1 production; however, AII-induced IP1 and Ca influx were enhanced by oxLDL. These effects were abolished by LOX-1 siRNA. Co-administration of oxLDL and AII upregulated aldosterone synthesis genes, such as CYP11B2; this effect was suppressed by a Gq inhibitor. In vivo, long-term AII and HFD administration increased adrenal CYP11B2 expression but not serum aldosterone levels. Conversely, short-term AII and oxLDL administration elevated serum aldosterone levels, but not CYP11B2 expression. These effects were absent in LOX-1 KO mice. Blood pressure was unaffected by HFD or oxLDL in both models. In conclusion, OxLDL enhances AII-induced aldosterone production in adrenal glands through LOX-1-AT1 interaction, although its impact on blood pressure regulation remains unclear. Oxidized LDL enhances Gq signaling and aldosterone production by angiotensin II via the AT1-LOX-1 receptor complex in adrenal cells. LOX-1 amplifies angiotensin II-induced aldosterone synthesis by modulating AT1 receptor signaling in adrenal glands. Co-stimulation with oxLDL enhances Gq activation via LOX-1-AT1 interaction, potentially through AT1 unique conformational changes. These findings underscore the interplay between dyslipidemia and RAAS in promoting hypertension and cardiovascular diseases.</p>","PeriodicalId":13029,"journal":{"name":"Hypertension Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}