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Fulltext Changes in the urinary metabolites in losartan-treated spontaneously hypertensive rats

Norasikin Ab Azis, Mohd Saleh Ahmad Kamal, Zurain Radjeni, Ahmed Mediani, Renu Agarwal

Journal of Clinical and Health Sciences, 2021;6(1):32-45.
MyJurnal

Introduction: This study examined the association of losartan induced changes in urinary
metabolomic profile with the changes in blood pressure (BP) and renin-angiotensinaldosterone system (RAAS) in spontaneously hypertensive rats (SHR). Methods: Male SHR
were administered with either 0.5 mL of distilled water (control group, n=6) or 10 mg.kg-1 of
losartan (group 2, n=6) daily by oral gavage for 4 weeks. Body weight, BP, food and water
intake were measured weekly. At week 4, urine was collected for urinary electrolyte analysis
and metabolite profiling, after which the animals were euthanised by decapitation and blood
was collected for analysis of components of RAAS and electrolyte concentrations. Urine
metabolite profile of SHR was determined using proton nuclear magnetic resonance (
1H-NMR)
spectrometry combined with multivariate data analysis. Results: At week 4, losartan-treated
SHR had significantly lower BP than non-treated SHR. There were no differences in water
and food intake, body weight, serum and urinary electrolyte concentrations or in their urinary
excretions between the two groups. No differences were evident in the components of RAAS
except that the angiotensinogen level was significantly higher in losartan-treated SHR
compared to non-treated SHR. Orthogonal partial least squares discriminant analysis (OPLSDA) showed clear separation of urinary metabolites between control and losartan-treated
SHR. Losartan-treated SHR group was separated from the control group by changes in the
intermediates involved in glycine, serine and threonine metabolism. Conclusion:
Antihypertensive effect of losartan in SHR seems to be associated with changes in urinary
metabolite profile, particularly involving the metabolism of glycine, serine and threonine.

Matched MeSH terms: Renin-Angiotensin System
Fulltext Can Renin-Angiotensin System Inhibitors Protect Against Acute Kidney Injury in Patients With COVID-19?

Kow CS, Ramachandram DS, Hasan SS

Crit Care Med, 2022 Nov 01;50(11):e796-e797.
PMID: 36227048 DOI: 10.1097/CCM.0000000000005618
Matched MeSH terms: Renin-Angiotensin System
Fulltext Gene Polymorphisms of the Renin-Angiotensin-Aldosterone System as Risk Factors for the Development of In-Stent Restenosis in Patients with Stable Coronary Artery Disease

Azova M, Timizheva K, Ait Aissa A, Blagonravov M, Gigani O, Aghajanyan A, et al.

Biomolecules, 2021 05 20;11(5).
PMID: 34065198 DOI: 10.3390/biom11050763

This study investigated the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms as possible genetic risk factors for the restenosis development in patients with drug-eluting stents. 113 participants had coronary artery disease and underwent stenting. The control group consisted of 62 individuals with intact coronary arteries. Patients were divided into two groups: with in-stent restenosis (ISR) and without it. The patients with ISR were classified into subgroups by the terms of the restenosis development and age. Real-time PCR and Restriction Fragment Length Polymorphism-PCR were used to genotype the study participants for RAAS gene polymorphisms. We found that the development of restenosis is generally associated with the minor A allele for renin (REN) rs2368564 and the major TT genotype for angiotensinogen (AGT) rs699. The heterozygous genotype for AGT rs4762 acts as a protective marker. A minor A allele for angiotensin II type 2 receptor (AGTR2) rs1403543 is associated with a risk of restenosis in people under 65 years old. Among patients with the early ISR, heterozygotes for angiotensin II type 1 receptor (AGTR1) rs5186 are more frequent, as well as A allele carriers for AGTR2 rs1403543. A minor homozygous genotype for REN rs41317140 and heterozygous genotype for aldosterone synthase (CYP11B2) rs1799998 are predisposed to the late restenosis. Thus, to choose the effective treatment tactics for patients with coronary artery disease, it is necessary to genotype patients for the RAAS polymorphisms, which, along with age and clinical characteristics, will allow a comprehensive assessment of the risk of the restenosis development after stenting.

Matched MeSH terms: Renin-Angiotensin System*
Fulltext COVID-19 and hypertension-evidence and practical management: Guidance from the HOPE Asia Network

Kario K, Morisawa Y, Sukonthasarn A, Turana Y, Chia YC, Park S, et al.

J Clin Hypertens (Greenwich), 2020 Jul;22(7):1109-1119.
PMID: 32643874 DOI: 10.1111/jch.13917

There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID-19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin-angiotensin system (RAS) inhibitors due to a key role of angiotensin-converting enzyme 2 receptors in the entry of the SARS-CoV-2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS-CoV-2 virus infection or worsens the course of COVID-19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID-19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N-terminal pro-B-type natriuretic peptide, D-dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID-19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well-being. For the ongoing management of patients with hypertension, telemedicine-based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID-19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.

Matched MeSH terms: Renin-Angiotensin System/drug effects
Fulltext Budget impact analysis of increasing prescription of renin-angiotensin system inhibitors drugs to standard anti-hypertensive treatments in patients with diabetes and hypertension in a hypothetical cohort of Malaysian population

Mohd-Tahir NA, Li SC

PLoS One, 2019;14(2):e0212832.
PMID: 30817790 DOI: 10.1371/journal.pone.0212832

INTRODUCTION: Renin-angiotensin system inhibitors (RAS) drugs have a proteinuria-reducing effect that could prevent the progression of kidney disease in diabetic patients. Our study aimed to assess the budget impact based on healthcare payer perspective of increasing uptake of RAS drugs into the current treatment mix of standard anti-hypertensive treatments to prevent progression of kidney disease in patient's comorbid with hypertension and diabetes.
METHODS: A Markov model of a Malaysian hypothetical cohort aged ≥30 years (N = 14,589,900) was used to estimate the total and per-member-per-month (PMPM) costs of RAS uptake. This involved an incidence and prevalence rate of 9.0% and 10.53% of patients with diabetes and hypertension respectively. Transition probabilities of health stages and costs were adapted from published data.
RESULTS: An increasing uptake of RAS drugs would incur a projected total treatment cost ranged from MYR 4.89 billion (PMPM of MYR 27.95) at Year 1 to MYR 16.26 billion (PMPM of MYR 92.89) at Year 5. This would represent a range of incremental costs between PMPM of MYR 0.20 at Year 1 and PMPM of MYR 1.62 at Year 5. Over the same period, the care costs showed a downward trend but drug acquisition costs were increasing. Sensitivity analyses showed the model was minimally affected by the changes in the input parameters.
CONCLUSION: Mild impact to the overall healthcare budget has been reported with an increased utilization of RAS. The long-term positive health consequences of RAS treatment would reduce the cost of care in preventing deterioration of kidney function, thus offsetting the rising costs of purchasing RAS drugs. Optimizing and increasing use of RAS drugs would be considered an affordable and rational strategy to reduce the overall healthcare costs in Malaysia.

Matched MeSH terms: Renin-Angiotensin System/drug effects