Displaying publications 1 - 20 of 45 in total

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  1. Balakumar P, Anand-Srivastava MB, Jagadeesh G
    Pharmacol Res, 2017 11;125(Pt A):1-3.
    PMID: 28711403 DOI: 10.1016/j.phrs.2017.07.003
    Matched MeSH terms: Renin-Angiotensin System/physiology*
  2. Parn KW, Ling WC, Chin JH, Lee SK
    Nutrients, 2022 Nov 01;14(21).
    PMID: 36364864 DOI: 10.3390/nu14214605
    This study aimed to identify the no-observed-adverse-effect level (NOAEL) of dietary epigallocatechin gallate (EGCG) supplementation and its possible antihypertensive and nutrigenomics effects in modulating intrarenal renin-angiotensin system (RAS) gene expression in spontaneously hypertensive rats (SHR). EGCG (50, 250, 500 or 1000 mg/kg b.w. i.g., once daily) was administered to SHR for 28 days. All the SHR survived with no signs of systemic toxicity. Increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and thiobarbituric acid reactive substances (TBARS) were evident in SHR supplemented with 500 and 1000 mg/kg b.w. but not in those supplemented with lower doses of EGCG. Subsequently, the NOAEL of EGCG was established at 250 mg/kg b.w., and the same protocol was replicated to assess its effects on blood pressure and renal RAS-related genes in SHR. The systolic blood pressure (SBP) of the EGCG group was consistently lower than the control group. The mRNA levels of cortical Agtr2 and Ace2 and medullary Agtr2, Ace and Mas1 were upregulated while medullary Ren was downregulated in EGCG group. Statistical analysis showed that SBP reduction was associated with the changes in medullary Agtr2, Ace, and Ren. Dietary EGCG supplementation exhibits antihypertensive and nutrigenomics effects through activation of intrarenal Ace and Agtr2 and suppression of Ren mediators, while a high dose of EGCG induced liver damage in SHR. In future clinical studies, liver damage biomarkers should be closely monitored to further establish the safety of the long-term use of EGCG.
    Matched MeSH terms: Renin-Angiotensin System*
  3. Loh HH, Lim QH, Chai CS, Goh SL, Lim LL, Yee A, et al.
    J Sleep Res, 2023 Feb;32(1):e13726.
    PMID: 36104933 DOI: 10.1111/jsr.13726
    Obstructive sleep apnea is a chronic, sleep-related breathing disorder, which is an independent risk factor for cardiovascular disease. The renin-angiotensin-aldosterone system regulates salt and water homeostasis, blood pressure, and cardiovascular remodelling. Elevated aldosterone levels are associated with excess morbidity and mortality. We aimed to analyse the influence and implications of renin-angiotensin-aldosterone system derangement in individuals with and without obstructive sleep apnea. We pooled data from 20 relevant studies involving 2828 participants (1554 with obstructive sleep apnea, 1274 without obstructive sleep apnea). The study outcomes were the levels of renin-angiotensin-aldosterone system hormones, blood pressure and heart rate. Patients with obstructive sleep apnea had higher levels of plasma renin activity (pooled wmd+ 0.25 [95% confidence interval 0.04-0.46], p = 0.0219), plasma aldosterone (pooled wmd+ 30.79 [95% confidence interval 1.05-60.53], p = 0.0424), angiotensin II (pooled wmd+ 5.19 [95% confidence interval 3.11-7.27], p renin levels) when studies involving patients with resistant hypertension were removed. Sub-group analysis demonstrated that levels of angiotensin II were significantly higher only among the Asian population with obstructive sleep apnea compared with those without obstructive sleep apnea. Body mass index accounted for less than 10% of the between-study variance in elevation of the renin-angiotensin-aldosterone system parameters. Patients with obstructive sleep apnea have higher levels of renin-angiotensin-aldosterone system hormones, blood pressure and heart rate compared with those without obstructive sleep apnea, which remains significant even among patients without resistant hypertension.
    Matched MeSH terms: Renin-Angiotensin System/physiology
  4. Pascale JV, Wolf A, Kadish Y, Diegisser D, Kulaprathazhe MM, Yemane D, et al.
    Adv Pharmacol, 2023;97:229-255.
    PMID: 37236760 DOI: 10.1016/bs.apha.2023.01.002
    Vascular function is dynamically regulated and dependent on a bevy of cell types and factors that work in concert across the vasculature. The vasoactive eicosanoid, 20-Hydroxyeicosatetraenoic acid (20-HETE) is a key player in this system influencing the sensitivity of the vasculature to constrictor stimuli, regulating endothelial function, and influencing the renin angiotensin system (RAS), as well as being a driver of vascular remodeling independent of blood pressure elevations. Several of these bioactions are accomplished through the ligand-receptor pairing between 20-HETE and its high-affinity receptor, GPR75. This 20-HETE axis is at the root of various vascular pathologies and processes including ischemia induced angiogenesis, arteriogenesis, septic shock, hypertension, atherosclerosis, myocardial infarction and cardiometabolic diseases including diabetes and insulin resistance. Pharmacologically, several preclinical tools have been developed to disrupt the 20-HETE axis including 20-HETE synthesis inhibitors (DDMS and HET0016), synthetic 20-HETE agonist analogues (20-5,14-HEDE and 20-5,14-HEDGE) and 20-HETE receptor blockers (AAA and 20-SOLA). Systemic or cell-specific therapeutic targeting of the 20-HETE-GPR75 axis continues to be an invaluable approach as studies examine the molecular underpinnings activated by 20-HETE under various physiological settings. In particular, the development and characterization of 20-HETE receptor blockers look to be a promising new class of compounds that can provide a considerable benefit to patients suffering from these cardiovascular pathologies.
    Matched MeSH terms: Renin-Angiotensin System*
  5. Siti-Zubaidah MZ, Harafinova HS, Liba AN, Nordin ML, Hambali KA, Siti HN
    Vascul Pharmacol, 2024 Sep;156:107414.
    PMID: 39089528 DOI: 10.1016/j.vph.2024.107414
    Sepsis and atherosclerotic cardiovascular disease (ASCVD) are major health challenges involving complex processes like inflammation, renin-angiotensin system (RAS) dysregulation, and thrombosis. Despite distinct clinical symptoms, both conditions share mechanisms mediated by bradykinin. This review explores bradykinin's role in inflammation, RAS modulation, and thrombosis in sepsis and ASCVD. In sepsis, variable kininogen-bradykinin levels may correlate with disease severity and progression, though the effect of bradykinin receptor modulation on inflammation remains uncertain. RAS activation is present in both diseases, with sepsis showing variable or low levels of Ang II, ACE, and ACE2, while ASCVD consistently exhibits elevated levels. Bradykinin may act as a mediator for ACE2 and AT2 receptor effects in RAS regulation. It may influence clotting and fibrinolysis in sepsis-associated coagulopathy, but evidence for an antithrombotic effect in ASCVD is insufficient. Understanding bradykinin's role in these shared pathologies could guide therapeutic and monitoring strategies and inform future research.
    Matched MeSH terms: Renin-Angiotensin System*
  6. Karim MM, Sultana S, Sultana R, Rahman MT
    J Infect Public Health, 2021 Nov;14(11):1686-1692.
    PMID: 34649043 DOI: 10.1016/j.jiph.2021.09.022
    As far as comorbidity is concerned, cardiovascular diseases (CVD) appear to be accounted for the highest prevalence, severity, and fatality among COVID 19 patients. A wide array of causal links connecting CVD and COVID-19 baffle the overall prognosis as well as the efficacy of the given therapeutic interventions. At the centre of this puzzle lies ACE2 that works as a receptor for the SARS-CoV-2, and functional expression of which is also needed to minimize vasoconstriction otherwise would lead to high blood pressure. Furthermore, SARS-CoV-2 infection seems to reduce the functional expression of ACE2. Given these circumstances, it might be advisable to consider a treatment plan for COVID-19 patients with CVD in an approach that would neither aggravate the vasodeleterious arm of the renin-angiotensinogen-aldosterone system (RAAS) nor compromise the vasoprotective arm of RAAS but is effective to minimize or if possible, inhibit the viral replication. Given the immune modulatory role of Zn in both CVD and COVID-19 pathogenesis, zinc supplement to the selective treatment plan for CVD and COVID-19 comorbid conditions, to be decided by the clinicians depending on the cardiovascular conditions of the patients, might greatly improve the therapeutic outcome. Notably, ACE2 is a zinc metalloenzyme and zinc is also known to inhibit viral replication.
    Matched MeSH terms: Renin-Angiotensin System
  7. Teh BT, Wan Azman WA, Thuraisingham S, Choy AM, Tan KH, Jesudason P, et al.
    JUMMEC, 1999;4:26-33.
    Activation of the synlpathetic nervous system (SNS) and renin-angiotensin system (RAS) plays a pivotal role in the pathophysiology and progression of the disease in chronic heart failure (CHF). Blocking the activation of the RAS with angiotensin converting enzyme inhibitors not only improves sylnptonls but also prolongs life in symptomatic CHF. Does a similar analogy hold true for the use of ß-blockers in CHF? Evidence from a number of small trials and several recent large prospective trials show that b-blockers may improve ventricular function and symptoms in CHF. In a combination of trials investigating the use of carvedilol (an α, and ß-blocker) in congestive heart failure a mortality benefit appears to be evident. There are still a number of key questions that relnaill unanswered regarding the tolerability, patient type and stage of CHF in which ß-blockers should be advocated. Several large scale trials are in progress to answer some of these questions and also to add further information regarding its efficacy and impact on survival. KEYWORDS: Beta-adrenoreceptor antagonist, congestive heart failure.
    Matched MeSH terms: Renin-Angiotensin System
  8. Kow CS, Ramachandram DS, Hasan SS
    Rev Port Cardiol, 2023 Sep;42(9):815-816.
    PMID: 37353197 DOI: 10.1016/j.repc.2023.04.008
    Matched MeSH terms: Renin-Angiotensin System
  9. Chee KH, Amudha K, Hussain NA, Haizal HK, Choy AM, Lang CC
    PMID: 14608517
    Conventional diuretic agents are very effective agents in relieving volume overload and congestive symptoms in chronic heart failure (CHF). However, they are associated with activation of the renin-angiotensin system (RAS) and the sympathetic nervous system and a reduction in glomerular filtration rate, all of which have been associated with adverse outcomes in CHF. Therefore, there is an increasing interest in drugs that target the natriuretic system without neurohormonal activation and deterioration of renal function. In this review, we will discuss the underlying rationale and evidence behind currently pursued strategies that target the natriuretic system. This includes the administration of natriuretic peptides (NPs) and strategies that potentiate the NP system, such as neutral endopeptidase inhibition. We will also highlight some potentially important interactions of these strategies with drugs that target the RAS.
    Matched MeSH terms: Renin-Angiotensin System/drug effects*
  10. Hian CK, Lee CL, Thomas W
    Nephron, 2016;134(2):59-63.
    PMID: 27476173 DOI: 10.1159/000448296
    Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a systemic disease characterised by the formation of multiple renal cysts that adversely affect renal function. ADPKD shows significant progression with age when complications due to hypertension are most significant. The activation of the renin-angiotensin-aldosterone system (RAAS) occurs in progressive kidney disease leading to hypertension. The RAAS system may also contribute to ADPKD progression by stimulating signalling pathways in the renal cyst cells to promote growth and deregulate epithelial transport. This mini review focuses on the contribution of the RAAS system to renal cyst enlargement and the potential for antagonists of the RAAS system to suppress cyst enlargement as well as control ADPKD-associated hypertension.
    Matched MeSH terms: Renin-Angiotensin System/drug effects*
  11. Hasan HA, AbuOdeh RO, Muda WAMBW, Mohamed HJBJ, Samsudin AR
    Diabetes Metab Syndr, 2017 Dec;11 Suppl 2:S531-S537.
    PMID: 28392355 DOI: 10.1016/j.dsx.2017.03.047
    AIMS: The aim was to investigate relationships of Vitamin D receptor gene (VDR) polymorphisms to the components of MetS among Arabs adult residing in the United Arab Emirates.

    METHODS: A cross-sectional study of 198 Arabs adult (50 males and 148 females). Serum levels of glucose, vitamin D, HDL-C, and TG, and blood pressure were measured. FokI, BsmI & TaqI genotyping of VDR were investigated using PCR-RFLP technique.

    RESULTS: Age of the participants was 21(9) years with a BMI of 26.8(7.8) kg/m2. About 15% had MetS with serum vitamin D levels of 25.5(18.2) nmol/L. VDR genotyping yielded: FokI: 57.1% FF and 38.9% Ff, BsmI: 29.8% bb and 51.5% Bb, while TaqI showed 39.4% TT and 43.4% Tt. The ff carriers had higher total cholesterol [174(12.4) mg/dl] than FF and Ff genotypes. Bb carriers showed higher BMI and LDL-C than BB and bb genotypes. In females, FokI VDR polymorphism showed significant association with systolic blood pressure (SBP) and F allele carriers were at higher risk of developing high SBP [x2=4.4, df1, OR=0.29 (95%CI: 0.087-0.98), p=0.035].

    CONCLUSION: VDR gene polymorphisms were not associated with MetS, yet it may affect the severity of some of components of MetS, namely the association of BsmI with obesity, FokI and BsmI with dyslipidemia and FokI with SBP.

    Matched MeSH terms: Renin-Angiotensin System/physiology
  12. Ong HT
    Singapore Med J, 2008 Aug;49(8):599-605; quiz 606.
    PMID: 18756340
    The comparative anti-hypertensive drug trials conducted to assess their cardiovascular protective efficacy actually produce compatible, not conflicting, results. In the last decade, there were 13 major comparative hypertension drug trials with the cardiovascular primary outcome being statistically equivalent in 11 of these 13 trials, involving over 90 percent of the randomised 168,593 patients. Where secondary outcomes favour a drug in these trials, that arm has a significantly lower treated blood pressure as in LIFE, VALUE, ASCOT and ALLHAT. Controversy occurs in seeking to attribute the benefit to drug effect; if the benefit is attributed to the lower achieved blood pressure, then the trials become consistent. The safety and value of diuretics, beta-blockers, calcium-blockers, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in reducing blood pressure, and in reducing clinical cardiovascular outcomes, is now clearly established. Overall, the importance of tight blood pressure control in reducing cardiovascular outcomes must be emphasised. Physicians should concentrate on achieving good blood pressure control, which often requires a combination of several antihypertensive drugs.
    Matched MeSH terms: Renin-Angiotensin System/drug effects
  13. Hasan SS, Kow CS, Hadi MA, Zaidi STR, Merchant HA
    Am J Cardiovasc Drugs, 2020 Dec;20(6):571-590.
    PMID: 32918209 DOI: 10.1007/s40256-020-00439-5
    INTRODUCTION: The use of renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), was alleged to cause a more severe course of novel coronavirus disease 2019 (COVID-19).

    METHODS: We systematically reviewed the published studies to assess the association of RAS inhibitors with mortality as well as disease severity in COVID-19 patients. A systematic literature search was performed to retrieve relevant original studies investigating mortality and severity (severe/critical disease) in COVID-19 patients with and without exposure to RAS inhibitors.

    RESULTS: A total of 59 original studies were included for qualitative synthesis. Twenty-four studies that reported adjusted effect sizes (24 studies reported mortality outcomes and 16 studies reported disease severity outcomes), conducted in RAS inhibitor-exposed and unexposed groups, were pooled in random-effects models to estimate overall risk. Quality assessment of studies revealed that most of the studies included were of fair quality. The use of an ACEI/ARB in COVID-19 patients was significantly associated with lower odds (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.56-0.95; n = 18,749) or hazard (hazard ratio [HR] = 0.75, 95% CI 0.60-0.95; n = 26,598) of mortality compared with non-use of ACEI/ARB. However, the use of an ACEI/ARB was non-significantly associated with lower odds (OR = 0.91, 95% CI 0.75-1.10; n = 7446) or hazard (HR = 0.73, 95% CI 0.33-1.66; n = 6325) of developing severe/critical disease compared with non-use of an ACEI/ARB.

    DISCUSSION: Since there was no increased risk of harm, the use of RAS inhibitors for hypertension and other established clinical indications can be maintained in COVID-19 patients.

    Matched MeSH terms: Renin-Angiotensin System/drug effects
  14. Sholehah, A. R., Ramle, A., Mohd Tajuddin, A., Wan Rohani, W. T., Jamilah, M. S., Razifah, M.
    MyJurnal
    The prevalence and incidence rate of hypertension among Orang Asli had been increasing due to
    modernization and assimilation of outside practices such as intake of high cholesterol food, alcohol, and
    smoking. Orang Asli utilize their herbs or plants to treat some illness due to the factor of logistics and the
    knowledge on these nature resources since decades ago that is carried out from their ancestors. In this review
    paper, hypertension genes of Orang Asli in Peninsular Malaysia and the utilization of ethno-medicinal plants
    in reducing the clinical manifestation in hypertension were deliberated. There are quite a number of related
    hypertensive genes particularly in renin-angiotensin-aldosterone system (RAAS) playing a pivotal role in
    pathogenesis of hypertension. A genome-wide association studies showed potential candidate genes in
    hypertension among Orang Asli in Peninsular Malaysia. However there is yet molecular study on these genes
    among Orang Asli with their unique genetic profile. Noteworthy information on mechanism of ethnomedicine in treating hypertension are scarce, even the efficacy of modern medicine in treating hypertension
    on Orang Asli are rare. Therefore, study on efficacy of ethno-medicine plant by Orang Asli and the
    regulation effect on hypertension genes are needed to be further explored and elucidated.
    Matched MeSH terms: Renin-Angiotensin System
  15. Joyce-Tan SM, Zain SM, Abdul Sattar MZ, Abdullah NA
    J Diabetes Res, 2016;2016:2161376.
    PMID: 26682227 DOI: 10.1155/2016/2161376
    Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls for AGT variants (P = 0.05) but not for ACE and AGTR1. Haplotype TCG of the AGT was associated with increased risk of T2DM (OR 1.92, 95% CI 1.15-3.20, permuted P = 0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of the AGT variants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk.
    Matched MeSH terms: Renin-Angiotensin System/genetics*
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