Assessing the evolution of hypertension management in Gansu, China: A comparative study of prevalence, awareness, treatment, and control in 2012 and 2022.

The aim of this study is to evaluate the developments in the treatment and prevalence of hypertension by demographic subgroups in least developed area of China in 2012 and 2022. This population-based cross-sectional study was conducted in 2012 and 2022, we applied stratified multistage random sampling to investigate residents aged 18 years or older in Gansu, the least developed province in the northwest of China. Questionnaires and anthropometric measurements were given to all respondents. The standardized prevalence of hypertension in adults in Gansu increased from 26.1% in 2012 to 28.8% in 2022. Compared with 2012, the control rate remains decreased despite the significantly improved awareness and treatment rates of hypertension in 2022. Apart from the reversal of the control rate, the trend of higher prevalence in men and higher awareness and treatment rates in women has not changed. There was an obviously increase in the proportion of participants who had received health education and hypertension management services from medical workers. The treatment was still primarily monotherapy, and there was no significant improvement in the prescription of medication. The prevalence of hypertension has increased mildly in the least developed region of China over the past decade, and the challenge of hypertension management has shifted from increasing awareness and treatment rates to increasing control rates. The onset and control of hypertension are affected by education methods, BMI, local economic conditions and other factors, and targeted strategies can be adopted to strengthen the management of hypertension in economically underdeveloped areas of China.

Dietary sodium/potassium intake and cognitive impairment in older patients with hypertension: Data from NHANES 2011-2014.

This study aimed to assess the relationship between dietary sodium/potassium intake and cognition in elderly individuals with hypertension. We designed a cross-sectional study based on the 2011-2014 National Health and Nutrition Examination Survey (NHANES) 2011-2014. A multivariable-logistic regression analysis was performed to analyze the relationship between sodium/potassium intake and cognitive impairment. Restricted cubic spline (RCS) based on regression analysis to assess the nonlinear dose-response relationship between dietary sodium intake and cognitive performance. Out of the 2276 participants included in this study, 1670 patients had hypertension. Compared with the lowest quartile of dietary sodium intake, the lowest weighted odds ratio of cognitive impairment in DSST was observed in Q4 (OR = 0.45, 0.29-0.70), and a similar trend was observed in AFT (OR = 0.34, 0.18-0.65). After adjusting the covariates, the lowest weighted multivariable-adjusted OR of cognitive impairment in DSST were also observed in Q4 (OR = 0.47, 0.26-0.84) compared with the lowest quartile of dietary sodium intake. The RCS results showed that dietary sodium intake was U-shaped and associated with the risk of cognitive impairment in the DSST (Pnon-linearity  = 0.0067). In addition, no significant association was observed between dietary potassium intake and different dimensions of cognitive performance. In conclusion, excessively high and low low dietary sodium were associated with impairment of specific processing speed, sustained attention, and working memory for elderly patients with hypertension in the United States. However, no association was observed between dietary potassium intake and cognition.

Effect of sacubitril/valsartan or valsartan on ventricular remodeling and myocardial fibrosis in perimenopausal women with hypertension.

OBJECTIVE: To evaluate the impact of sacubitril/valsartan on blood pressure (BP), ventricular structure, and myocardial fibrosis compared with valsartan in perimenopausal hypertensive women. METHODS: This prospective, randomized, actively controlled, open-label study included 292 women with perimenopausal hypertension. They were randomly divided into two groups: sacubitril/valsartan 200 mg once daily and valsartan 160 mg once daily for 24 weeks. The relevant indicators of ambulatory BP, echocardiography, and myocardial fibrosis regulation were assessed at baseline and at 24 weeks. RESULTS: The 24-h mean SBP after 24 weeks of treatment was 120.08 ±â€Š10.47 mmHg in the sacubitril/valsartan group versus 121.00 ±â€Š9.76 mmHg in the valsartan group ( P  = 0.457). After 24 weeks of treatment, there was no difference in central SBP between the sacubitril/valsartan and valsartan groups (117.17 ±â€Š11.63 versus 116.38 ±â€Š11.58, P  = 0.568). LVMI in the sacubitril/valsartan group was lower than that in the valsartan group at week 24 ( P  = 0.009). LVMI decreased by 7.23 g/m 2 from the baseline in the sacubitril/valsartan group and 3.70 g/m 2 in the valsartan group at 24 weeks ( P  = 0.000 versus 0.017). A statistically significant difference in LVMI between the two groups was observed at 24 weeks after adjusting for the baseline LVMI ( P  = 0.001). The levels of α-smooth muscle actin (α-SMA), connective tissue growth factor (CT-GF) and transforming growth factor-ß (TGF-ß) were reduced in the sacubitril/valsartan group compared with the baseline ( P  = 0.000, 0.005, and 0.000). LVMI between the two groups was statistically significant at 24 weeks after correcting for confounding factors 24-h mean SBP and 24-h mean DBP ( P  = 0.005). The LVMI, serum TGF-ß, α-SMA, and CT-GF remained statistically significant between the two groups after further correcting the factors of age, BMI, and sex hormone levels ( P  < 0.05). CONCLUSION: Sacubitril/valsartan could reverse ventricular remodeling more effectively than valsartan. The different effects of these two therapies on ventricular remodeling in perimenopausal hypertensive women might be because of their different effects on the down-regulation of fibrosis-related factors.

Corrigendum: Research on the mechanism and prevention of hypertension caused by apatinib through the RhoA/ROCK signaling pathway in a mouse model of gastric cancer.

[This corrects the article DOI: 10.3389/fcvm.2022.873829.].

Identification and immune characteristics of molecular subtypes related to protein glycosylation in Alzheimer's disease.

Background: Protein glycosylation has been confirmed to be involved in the pathological mechanisms of Alzheimer's disease (AD); however, there is still a lack of systematic analysis of the immune processes mediated by protein glycosylation-related genes (PGRGs) in AD. Materials and methods: Transcriptomic data of AD patients were obtained from the Gene Expression Omnibus database and divided into training and verification datasets. The core PGRGs of the training set were identified by weighted gene co-expression network analysis, and protein glycosylation-related subtypes in AD were identified based on k-means unsupervised clustering. Protein glycosylation scores and neuroinflammatory levels of different subtypes were compared, and functional enrichment analysis and drug prediction were performed based on the differentially expressed genes (DEGs) between the subtypes. A random forest model was used to select important DEGs as diagnostic markers between subtypes, and a line chart model was constructed and verified in other datasets. We evaluated the differences in immune cell infiltration between the subtypes through the single-sample gene set enrichment analysis, analyzed the correlation between core diagnostic markers and immune cells, and explored the expression regulation network of the core diagnostic markers. Results: Eight core PGRGs were differentially expressed between the training set and control samples. AD was divided into two subtypes with significantly different biological processes, such as vesicle-mediated transport in synapses and neuroactive ligand-receptor interactions. The high protein glycosylation subtype had a higher level of neuroinflammation. Riluzole and sulfasalazine were found to have potential clinical value in this subtype. A reliable construction line chart model was constructed based on nine diagnostic markers, and SERPINA3 was identified as the core diagnostic marker. There were significant differences in immune cell infiltration between the two subtypes. SERPINA3 was found to be closely related to immune cells, and the expression of SERPINA3 in AD was found to be regulated by a competing endogenous RNA network that involves eight long non-coding RNAs and seven microRNAs. Conclusion: Protein glycosylation and its corresponding immune process play an important role in the occurrence and development of AD. Understanding the role of PGRGs in AD may provide a new potential therapeutic target for AD.

Research on the Mechanism and Prevention of Hypertension Caused by Apatinib Through the RhoA/ROCK Signaling Pathway in a Mouse Model of Gastric Cancer.

Hypertension is one of the main adverse effects of antiangiogenic tumor drugs and thus limits their application. The mechanism of hypertension caused by tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factors is mainly related to inhibition of the nitric oxide (NO) pathway and activation of the endothelin pathway, as well as vascular rarefaction and increased salt sensitivity; consequently, prevention and treatment differ for this type of hypertension compared with primary hypertension. Apatinib is a highly selective TKI approved in China for the treatment of advanced or metastatic gastric cancer. The RhoA/ROCK pathway is involved in the pathogenesis of hypertension and mediates smooth muscle contraction, eNOS inhibition, endothelial dysfunction and vascular remodeling. In this study, in vivo experiments were performed to explore whether the RhoA/ROCK signaling pathway is part of a possible mechanism of apatinib in the treatment of gastric cancer-induced hypertension and the impairment of vascular remodeling and left ventricular function. Y27632, a selective small inhibitor of both ROCK1 and ROCK2, was combined with apatinib, and its efficacy was evaluated, wherein it can reduce hypertension induced by apatinib treatment in gastric cancer mice and weaken the activation of the RhoA/ROCK pathway by apatinib and a high-salt diet (HSD). Furthermore, Y-27632 improved aortic remodeling, fibrosis, endothelial dysfunction, superior mesenteric artery endothelial injury, left ventricular dysfunction and cardiac fibrosis in mice by weakening the activation of the RhoA/ROCK pathway. The expression of RhoA/ROCK pathway-related proteins and relative mRNA levels in mice after apatinib intervention were analyzed by various methods, and blood pressure and cardiac function indexes were compared. Endothelial and cardiac function and collagen levels in the aorta were also measured to assess vascular and cardiac fibrosis and to provide a basis for the prevention and treatment of this type of hypertension.

Apatinib Through Activating the RhoA/ROCK Signaling Pathway to Cause Dysfunction of Vascular Smooth Muscle Cells.

Vascular smooth muscle cells (VSMCs) are associated with differentiated, organized, and contractile phenotype under the effect of various types of physiological conditions those are associated with migratory, proliferative, and synthetic phenotype under the effect of various types of stimuli, which dysfunction drives many cardiovascular diseases. Abnormal cell proliferation and invasion of VSMCs are among the primary causes of hypertension. Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) that highly selectively binds to and strongly inhibits VEGFR-2. Previous studies have confirmed that the TKIs can raise blood pressure through RhoA/ROCK pathway. LARG is a key gene in the RhoA/ROCK pathway and plays a critical role in the continuous vasoconstriction function because it regulates part of signal transduction in VSMCs. In this study, an in vitro experiment was conducted to observe that apatinib caused dysfunction of MOVAS cells through the RhoA/ROCK signalling pathway and Y27632, a nonspecific ROCK inhibitor, and knockout of LARG gene can improve the proliferation, antiapoptosis, oxidative stress, and mitochondrial autophagy of apatinib-induced MOVAS cells. These findings suggest that activation of the RhoA/ROCK signalling pathway could be the underlying mechanism of apatinib-induced dysfunction of MOVAS cells, while ROCK inhibitor and knockout of LARG gene have potential therapeutic value.

Effect of different treatments for obstructive sleep apnoea on blood pressure.

OBJECTIVE: Obstructive sleep apnoea (OSA) is a common cause of secondary hypertension. This network meta-analysis (NMA) assessed the effect of different OSA treatments on lowering blood pressure. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for relevant randomized controlled trials. The search strategies included the concepts of OSA, blood pressure, hypertension, and blood pressure-reducing treatments without language or data restriction (from inception to 1 June 2021). The outcomes included office SBP, office DBP, daytime SBP (dSBP) and DBP (dDBP), and night-time SBP (nSBP) and DBP (nDBP). A Bayesian network meta-analysis was performed, and mean differences with 95% credibility intervals were calculated. RESULTS: We reviewed 49 randomized controlled trials involving 4893 patients and the following interventions: continuous positive-airway pressure (CPAP), mandibular advancement devices, nocturnal supplemental oxygen, surgery, ß-blocker, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), renal sympathetic denervation (RDN), mineralocorticoid receptor antagonists (MRAs), calcium channel blockers. MRAs were significantly associated with blood pressure reduction followed by ACEI/ARB. RDN could reduce office SBP, office DBP, 24-h SBP, 24-h DBP, dSBP, and dDBP. CPAP also demonstrated modest blood pressure lowering. CONCLUSION: MRAs and ACEIs/ARBs can reduce blood pressure effectively in patients with OSA. RDN is a novel hypertension treatment that lowered blood pressure in such patients. CPAP was associated with mild but stable blood pressure reduction, and it might be helpful as an adjunctive therapy in OSA patients with hypertension. REVIEW REGISTRATION: This systematic review and meta-analysis was registered in PROSPERO: CRD42021240891.

PTEN inhibitor attenuates cardiac fibrosis by regulating the M2 macrophage phenotype via the PI3K/AKT/TGF-ß/Smad 2/3 signaling pathway.

Cardiac fibrosis is a key feature of hypertensive cardiac remodeling. In response to microenvironmental stimuli, phenotypic and functional changes in macrophages are considered important determinants of cardiac fibrosis attenuation. VO-OHpic, a phosphatase and tension homolog of chromosome 10 (PTEN) inhibitor, has been demonstrated to be cardioprotective in cardiac remodeling. However, whether VO-OHpic can improve cardiac fibrosis and macrophage polarization remains elusive. The interaction between VO-OHpic and the macrophage phenotype to attenuate cardiac fibrosis was studied in both spontaneously hypertensive rats in vivo and an Ang II-induced hypertension model in vitro. In vitro experiments showed that VO-OHpic promoted M2 macrophage polarization and markedly inhibited proinflammatory M1 macrophages, while VO-OHpic treatment of protein kinase B (AKT)-knockdown/LY294002 (a PI3K inhibitor) macrophages exerted a reduced effect. In a coculture system, culturing cardiac fibroblasts with VO-OHpic-treated macrophages led to significant suppression of proliferation, fibrotic marker expression, and transforming growth factor (TGF)-ß and Smad 2/3 protein expression. Taken together, VO-OHpic mediated a fibro-protective effect and increased M2 macrophage polarization via the phosphatidylinositol 3-kinase (PI3K)/AKT/TGF-ß/Smad2/3 pathway.

Rho kinase inhibition ameliorates vascular remodeling and blood pressure elevations in a rat model of apatinib-induced hypertension.

OBJECTIVES: Hypertension is one of the major adverse effects of tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factors. However, the mechanism underlying TKIs-induced hypertension remains unclear. Here, we explored the role of the RhoA/Rho kinase (ROCK) signaling pathway in elevation of blood pressure (BP) induced by apatinib, a selective TKI approved in China for treatment of advanced or metastatic gastric cancer. A nonspecific ROCK inhibitor, Y27632, was then combined with apatinib and its efficacy in alleviating apatinib-induced hypertension was evaluated. METHODS: Normotensive female Wistar-Kyoto rats were exposed to two different doses of apatinib, or apatinib combined with Y27632, or vehicle for 2 weeks. BP was monitored by a tail-cuff plethysmography system. The mRNA levels and protein expression in the RhoA/ROCK pathway were determined, and vascular remodeling assessed. RESULTS: Administration of either a high or low dose of apatinib was associated with a rapid rise in BP, reaching a plateau after 12 days. Apatinib treatment mediated upregulation of RhoA and ROCK II in the mid-aorta, more significant in the high-dose group. However, ROCK I expression showed no statistically significant differences. Furthermore, the mRNA level of GRAF3 decreased dose-dependently. Apatinib administration was also associated with decreased levels of MLCP, and elevated endothelin-1 (ET-1) and collagen I, which were accompanied with increased mid-aortic media. However, treatment with Y27632 attenuated the above changes. CONCLUSION: These findings suggest that activation of the RhoA/ROCK signaling pathway could be the underlying mechanism of apatinib-induced hypertension, while ROCK inhibitor have potential therapeutic value.

The effect of exercise training and physiotherapy on diastolic function, exercise capacity and quality of life in patients with heart failure with preserved ejection fraction: a systematic review and meta-analysis.

BACKGROUND: Exercise and physiotherapy are accepted as an important contribution to the rehabilitation of patients with heart failure with preserved ejection fraction (HFpEF). But the previous results are unclear partly because of their limited power and small sample sizes. AIMS: We aimed to understand better the effects of two exercise training interventions and two modalities of physiotherapies on exercise capacity, quality of life (QoL), and diastolic dysfunction in HFpEF patients. METHODS: The Cochrane Library, EMBASE, and MEDLINE via PubMed were searched for randomized controlled trials from their inception to May 2021. The effect size was estimated as mean differences (MD) with 95% confidence intervals (CI). RESULTS: A total of 14 articles on 13 trials were included in this meta-analysis with 673 HFpEF patients. The pooling revealed that peak oxygen uptake was improved by endurance training, functional electrical stimulation (FES), and inspiratory muscle training (IMT). Similar results were observed for a 6-minute walk test and QoL. A combination of endurance and resistance training (combined exercise) was beneficial to the ratio of peak early to late diastolic mitral inflow velocities (MD [95% CI]: -2.90 [-4.97, -0.83]; P = 0.006) and the early diastolic mitral annual velocity (MD [95% CI]: 1.40 [0.68, 2.12]; P = 0.006]. IMT improved the ventilation/carbon dioxide ratio slope (MD [95% CI]: -3.36 ml/kg/min [-6.17, -0.54]; P = 0.019]. CONCLUSIONS: FES and IMT improve functional capacity and QoL without a change in diastolic function in HFpEF patients, and the outcomes are similar to endurance training. Notably, combined exercise may improve diastolic function. Key words: diastolic function, exercise training, functional electrical stimulation, heart failure with preserved ejection fraction, inspiratory muscle training.

Effect of free androgen index on blood pressure variability and target organ damage in postmenopausal hypertensive women: findings from a cross-sectional study.

OBJECTIVE: The present study investigated the effects of free androgen index (FAI) on ambulatory blood pressure (ABP) and target organ function in postmenopausal hypertensive women. METHODS: A total of 285 postmenopausal hypertensive women (mean age 54.06 ±â€Š3.61) were admitted to the Department of Hypertension of Lanzhou University Second Hospital between December 2018 and December 2020. According to the serum FAI level, the participants were divided into a low-FAI (<0.15) group, a medium-FAI (0.15-0.2) group, and a high-FAI (>0.2) group. The relationship of FAI with 24-hour ABP, left ventricular mass index (LVMI), and cardio-ankle vascular index (CAVI) was analyzed. RESULTS: The LVMI, CAVI, 24-hour mean systolic blood pressure (SBP), 24-hour SBP coefficient of variation and 24-hour SBP standard deviation, 24-hour SBP average real variation (ARV), and 24-hour diastolic blood pressure (DBP) ARV in high-FAI group were significantly higher than those in low- and medium-FAI groups (P < 0.05). After adjusting for confounding factors, partial correlation analysis showed that FAI was positively correlated with LVMI (r = 0.728, P < 0.001), CAVI (left: r = 0.718, P < 0.001; right: r = 0.742, P < 0.001), 24-hour SBP ARV (r = 0.817, P < 0.001), and 24-hour DBP ARV (r = 0.747, P < 0.001). After adjusting for confounding factors, it was found that LVMI increased by 17.64 g/m2 for every 1 unit increase in FAI. CAVI also increased by 8.983 for every additional unit of FAI. In addition, the results also showed that LVMI and CAVI decreased respectively by 0.198 g/m2 and 0.009 for every 1 unit increase in sex hormone-binding globulin. Multivariable linear regression showed that FAI was an independent risk factor for 24-hour SBP ARV (OR: 20.416, 95% CI 8.143-32.688, P = 0.001) and 24-hour DBP ARV (OR: 16.539, 95% CI 0.472-32.607, P = 0.044). The results also showed that sex hormone-binding globulin was an independent factor of 24-hour SBP ARV (OR: -0.022, 95% CI -0.044 to 0.000, P = 0.048) and 24-hour DBP-ARV (OR: -0.018, 95% CI -0.029 to -0.008, P = 0.001). CONCLUSION: Higher serum FAI levels in postmenopausal hypertensive women indicate abnormal BP regulation and more serious target organ damage. FAI is closely related to 24-hour SBP ARV and 24-hour DBP ARV in postmenopausal hypertensive women.

A narrative review on the interaction between genes and the treatment of hypertension and breast cancer.

OBJECTIVE: The aim to discuss the close relationship between the common biological mechanisms of breast cancer and hypertension, inflammation and oxidative stress, breast cancer gene mutations breast cancer susceptibility gene (BRCA), G protein-coupled receptor kinase (GRK4), etc. and breast cancer treatment includes chemotherapy, Endocrine therapy, Targeted therapy and anti-angiogenesis drugs. In anti-angiogenesis drugs focusing on the mechanism of tyrosine kinase inhibitors (TKI) that may activate the rhoa/rock pathway to cause hypertension, as well as the relationship between breast cancer and antihypertensive drugs includes angiotensin-converting enzyme inhibitors (ACEIs), Calcium channel blockers (CCBs) and ß-blockers (BBs)will be explored. BACKGROUND: Cardiovascular diseases (CVD) and tumors are the two major types of diseases with the highest mortality rates, while hypertension accounts for the largest proportion of CVDs. A large number of the same or similar risk factors are shared between hypertension and tumors, and they influence each other. Many patients, particularly elderly patients, often present with the coexistence of the two diseases. As medical advances have enabled clinicians to cure tumors, many patients with cancer live longer, leading to a gradual increase in the incidence of CVDs, including hypertension. With the second highest incidence among tumors, breast cancer has gradually attracted widespread attention and has been the topic of numerous studies. Studies have confirmed that CVD is one of the causes of death in elderly patients with breast cancer. METHODS: Publications from 1985 to 2020 were retrieved from the Web Of Science, Cochrane Library, PubMed, EMBASE and MEDLINE database. We used a mix of MeSH and keywords. CONCLUSIONS: Hypertension and cancer may share a common mechanism. The screening and risk assessment of breast cancer in patients with hypertension must be strengthened. Breast cancer cardiology is the interdisciplinary study of oncology and cardiology, and in-depth research in this field may result in long-term improvements in the survival and prognosis of patients with both clinical hypertension and breast cancer.

Albuminuria and Dipstick Proteinuria for Predicting Mortality in Heart Failure: A Systematic Review and Meta-Analysis.

Background: Research suggest that albuminuria is not only an independent risk factor for the development of heart failure but may also act as a biomarker for predicting adverse outcomes. To date, no study has synthesized evidence on its role as a prognostic indicator. Thus, the current study aimed to quantitatively assess the prognostic utility of albuminuria as well as dipstick proteinuria in predicting mortality in heart failure patients. Methods: PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched up to October 10, 2020. All studies reporting multivariable-adjusted hazard ratios (HR) for albuminuria or dipstick proteinuria for mortality and/or hospitalization in heart failure patients were included. Results: Eleven studies were included. Seven assessed albuminuria and five assessed dipstick proteinuria. Our analysis revealed a statistically significant increased risk of all-cause mortality with microalbuminuria (HR: 1.54; 95% CI, 1.23-1.93; I 2 = 79%; p = 0.0002) and macroalbuminuria (HR: 1.76; 95% CI, 1.21-2.56; I 2 = 88%; p = 0.003) in heart failure patients. The risk of all-cause mortality and hospitalization was also significantly increased with macroalbuminuria. Microalbuminuria was associated with significantly increased cardiovascular mortality and combined cardiovascular mortality and hospitalization. Positive dipstick test for proteinuria was significantly associated with mortality in heart failure (HR: 1.54; 95% CI, 1.28-1.84; I 2 = 67%; p < 0.00001). Conclusion: Both microalbuminuria and macroalbuminuria are predictors of mortality in patients with heart failure. Dipstick proteinuria may be used as a rapid screening test to predict mortality in these patients.

Comparative efficacy of different types of antihypertensive drugs in reversing left ventricular hypertrophy as determined with echocardiography in hypertensive patients: A network meta-analysis of randomized controlled trials.

Reversing left ventricular hypertrophy (LVH) can reduce the incidence of adverse cardiovascular events. However, there is no clear superiority-inferiority differentiation between angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers (BB), calcium channel blockers (CCB), and diuretics in reversing LVH in hypertensive patients. To provide further evidence for choosing the optimal antihypertensive drug for improving LVH, we performed a network meta-analysis of randomized controlled trials (RCTs) based on the Cochrane library database, Embase, and Pubmed, and identified 49 studies involving 5402 patients that were eligible for inclusion. It was found that ARB could improve LVH in hypertensive patients more effectively than CCB (MD -4.07, 95%CI -8.03 to -0.24) and BB (MD -4.57, 95%CI -8.07 to -1.12). Matched comparison of renin-angiotensin system inhibitors (RASi) showed that the effect of ACEI in reducing left ventricular mass index (LVMi) was not effective as that of ARB (MD -3.72, 95%CI -7.52 to -0.11). The surface under the cumulative ranking for each intervention indicated that the use of ARB was more effective among the different types of antihypertensive drugs (97%). This network meta-analysis revealed that the use of ARB in antihypertensive therapy could achieve better efficacy in reversing LVH in hypertensive patients.

Protective effects of irbesartan and benazepril against vaginal vascular remodeling and fibrosis in female spontaneously hypertensive rats.

OBJECTIVE: To compare the potential beneficial effects of the angiotensin converting enzyme inhibitor (ACEI) benazepril and the angiotensin II receptor 1 blocker (ARB) irbesartan on vaginal vascular remodeling and fibrosis in female spontaneously hypertensive rats (SHRs). METHODS: Twelve-week-old female SHRs were treated with irbesartan or benazepril for 12 weeks. Vaginal renin angiotensin system (RAS) components were detected by polymerase chain reaction and western blot and vaginal α-smooth muscle actin (α-SMA), endothelial nitric oxide synthase (eNOS), and collagen III (Col III) were analyzed by western blot. Vaginal tissue sections were examined by hematoxylin and eosin staining, Masson trichrome staining, and immunohistochemical analysis of α-SMA and Col III. RESULTS: Irbesartan and benazepril had different impacts on vaginal RAS components. Both agents decreased vaginal α-SMA and Col III and increased eNOS expression in SHR. The wall/lumen thickness ratio of vaginal arterioles was similarly decreased following irbesartan and benazepril treatment. Both drugs also decreased collagen deposition in SHRs. There was no difference in vaginal vascular remodeling or fibrosis between the two groups. CONCLUSIONS: Irbesartan and benazepril have different effects on vaginal RAS expression but similar positive effects against vaginal vascular remodeling and fibrosis.

Effects of Angiotensin-Converting Enzyme Inhibitors on Arterial Stiffness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

To determine the effects of ACEIs on arterial stiffness, a meta-analysis of randomized controlled trials was conducted. Relevant articles that investigated the effects of ACEIs on arterial stiffness from PubMed, Embase, and the Cochrane library from inception to September 2018 were systematically retrieved. The investigated outcomes included brachial-ankle pulse wave velocity (ba-PWV) and carotid-femoral PWV (cf-PWV) by using weighted mean differences (WMDs) and 95% confidence intervals (CIs) with the random-effects model. A total of 17 RCTs including 1,458 individuals were included. The summary results indicated no significant differences between ACEIs and control for ba-PWV and cf-PWV. Also, no significant differences between ACEI and control for ba-PWV and cf-PWV were observed in hypertensive patients, while the therapeutic effects of ACEI versus placebo showed statistically significant difference. Moreover, subgroup analysis indicated that the levels of ba-PWV were significantly associated if the study was conducted in Western countries, mean age <60.0 years, percentage male ≥60.0%, compared with ARBs, baseline PWV <10.0, and high-quality study. Furthermore, the significant levels of cf-PWV in patients who received ACEIs were observed when percentage male was ≥60.0% and the studies were of high-quality. Finally, no significant differences were observed between ACEIs and other antihypertensive drugs regarding the changes of systolic blood pressure (SBP) and diastolic blood pressure (DBP). The overall analysis suggested no significant differences between ACEIs and other antihypertensive drugs for ba-PWV and cf-PWV levels, whereas ACEIs versus placebo showed lower levels of ba-PWV and cf-PWV.

Effects of Tetrahydrobiopterin Combined with Nebivolol on Cardiac Diastolic Function in SHRs.

This study aimed to evaluate the effects of combined use of tetrahydrobiopterin (BH4) and nebivolol on cardiac diastolic dysfunction in spontaneously hypertensive rats (SHRs). Twelve-week-old male SHRs were treated with BH4, nebivolol, or a combination of both. Left ventricle function was evaluated, and reactive oxygen species (ROS) production (including dihydroethidium (DHE) and 3-nitrotyrosine (3-NT)), nitric oxide synthase (NOS) activity and the level of NO in myocardial tissue were determined. The expression levels of endothelial NOS (eNOS), phospholamban (PLN), sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ß3-adrenoceptor, cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG) were assayed. Treatment with BH4, nebivolol, or both reversed the noninvasive indexes of diastolic function, including E/E' and E'/A', and the invasive indexes, including time constant of isovolumic left ventricle (LV) relaxation (tau), -dP/dtmin, -dP/dtmin/LV systolic pressure (LVSP), and LV end-diastolic pressure (LVEDP) in SHRs. mRNA and protein expression levels of eNOS dimer, phosphorylated PLN, SERCA2a, cGMP, and PKG in the myocardium of treated SHRs were significantly up-regulated compared with those in control rats (p < 0.05 or p < 0.01). The expression levels of 3-NT and DHE were reduced in all treated groups (p < 0.05 or p < 0.01). Notably, combined use of BH4 and nebivolol had better cardioprotective effects than monotherapies. BH4 or nebivolol has a protective effect on diastolic dysfunction in SHRs, and BH4 combined with nebivolol may exert a synergistically cardioprotective effect through activation of ß3-adrenoceptor and the NO/cGMP/PKG signaling pathway.