Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy

Ghazi, Lama; Drawz, Paul

doi:10.12688/f1000research.9692.1

Cited by 55 publications

(60 citation statements)

References 99 publications

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“…There are well-established drugs that interfere with RAAS at several sites, including (1) ACEIs, (2) ARBs, (3) direct renin inhibitors (DRIs), (4) mineralocorticoid receptor antagonists (MRAs), and even (5) beta blockers, the last of which may be considered partial inhibitors (Ghazi, Drawz, 2017;Ferrari, 2013). ACEIs and ARBs have been the cornerstone of RAAS inhibition for years and are key therapeutic options in patients with hypertension, reducing cardiovascular morbidity and mortality and improving renal outcomes (Ghazi, Drawz, 2017).…”

Section: Renin-angiotensin Aldosterone Systemmentioning

confidence: 99%

“…ACEIs and ARBs have been the cornerstone of RAAS inhibition for years and are key therapeutic options in patients with hypertension, reducing cardiovascular morbidity and mortality and improving renal outcomes (Ghazi, Drawz, 2017). However, inhibition of RAAS with ACEIs or ARBs has proven effective for controlling hypertension most important handicap of these agents is incomplete blockage of RAAS.…”

Section: Renin-angiotensin Aldosterone Systemmentioning

confidence: 99%

“…Renin has a unique specificity for its substrate angiotensin. Inhibition of renin provides an attractive option to inhibit the RAAS from its origin (Ghazi, Drawz, 2017). By complete blockage of RAAS at its origin, decrease in both Ang I and Ang II levels can be achieved by DRIs.…”

Section: Fig 1 Schematic Representation Of the Renin-angiotensin-almentioning

confidence: 99%

“…The development of DRI started more than 30 years ago (Ghazi, Drawz, 2017). The first synthetic renin inhibitor was pepstatin, which was followed by first-generation agents that were active but required parenteral administration.…”

Section: Fig 1 Schematic Representation Of the Renin-angiotensin-almentioning

confidence: 99%

“…Aliskiren,an octanamide, is the first (approved in 2007) of a new class of completely non-peptide, low-molecular-weight (609.8 Da), orally active transition-state renin inhibitors and only approvedfor the treatment of hypertension (Pantzaris, Karanikolas, Tsiotsios, Velissaris, 2017;Nissenson, Fine, 2017), and a significant BP reduction has been demonstrated in patients with essential HT with no rebound effects on BP after the withdrawal of the treatment (Ghazi, Drawz, 2017;Wal, Rai, Dixit, 2011).…”

Section: Blood Pressure Lowering With Aliskirenmentioning

confidence: 99%

See 4 more Smart Citations

Direct Renin Inhibitors in Arterial Hypertension Treatment

Meretskyi

Meretska

Kulyanda

et al. 2017

SJPU

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Abstract. High blood pressurewas the leading cause of death and disability-adjusted life years worldwide. Despite progress in treatment of hypertension, a number of people with uncontrolled or resistant hypertension increases. Hypertensive disorders are strongly linked with an overactive renin-angiotensin aldosterone system. The renin-angiotensin-aldosterone system has been a highly successful pharmacologic target, as the system is strongly implicated in the development of hypertension-related target organ damage.renin-angiotensin aldosterone systemrenin-angiotensin aldosterone system Aliskiren, an octanamide, is the firstof a new class of completely non-peptide, low-molecular-weight, orally active transitionstate renin inhibitors and only approved for the treatment of hypertension.

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Section: Renin-angiotensin Aldosterone Systemmentioning

confidence: 99%

Section: Renin-angiotensin Aldosterone Systemmentioning

confidence: 99%

Section: Fig 1 Schematic Representation Of the Renin-angiotensin-almentioning

confidence: 99%

Section: Fig 1 Schematic Representation Of the Renin-angiotensin-almentioning

confidence: 99%

Section: Blood Pressure Lowering With Aliskirenmentioning

confidence: 99%

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Direct Renin Inhibitors in Arterial Hypertension Treatment

Meretskyi

Meretska

Kulyanda

et al. 2017

SJPU

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The Bioequivalence Between Valsartan Oral Solution and Suspension Formulations Developed for Pediatric Use

Sivasubramanian

Sunkara

Karan

et al. 2022

Clinical Pharm in Drug Dev

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The bioequivalence of valsartan 160 mg oral solution compared to suspension was assessed in a single‐dose, open‐label, randomized, 2‐period, 2‐way crossover study in 82 healthy adults. The participants were randomly assigned (1:1) to receive a single dose of the solution or suspension formulation in each of the two treatment periods. Serial blood samples for pharmacokinetic evaluation were collected up to 48 hours post‐dose. The pharmacokinetic parameters were estimated by noncompartmental methods and analyzed as per bioequivalence criteria of statistical analysis. The peak plasma concentration of valsartan was reached with median time of 1 and 3 hours with solution and suspension formulation, respectively. Compared to suspension formulation, the mean peak plasma concentration with solution formulation was higher by 32% (90%CI, 1.27‐1.38) while the geometric mean ratios (1.09) and the associated 90%CIs (1.05‐1.13) of both the areas under the concentration time‐curves (from time zero to the last quantifiable concentration and from time zero to infinity) were contained in the required range of 0.80 to 1.25. No new safety signals were observed with either of the formulations.

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Exposure to low dose of Bisphenol A (BPA) intensifies kidney oxidative stress, inflammatory factors expression and modulates Angiotensin II signaling under hypertensive milieu

Nagarajan,

Maadurshni,

Manivannan

2023

J Biochem & Molecular Tox

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Humans are constantly exposed to low concentrations of ubiquitous environmental pollutant, Bisphenol A (BPA). Due to the prevalence of hypertension (one of the major risk factors of cardiovascular disease [CVD]) in the population, it is necessary to explore the adverse effect of BPA under hypertension associated pathogenic milieu. The current study exposed the Nω‐nitro‐l‐arginine methyl ester (L‐NAME) induced hypertensive Wistar rats to low dose BPA (50 μg/kg) for 30 days period. In tissue samples immunohistochemistry, real‐time quantitative polymerase chain reaction and enzymatic assays were conducted. Moreover, studies on primary kidney cell culture were employed to explore the impact of low dose of BPA exposure at nanomolar level (20−80 nM range) on renal cells through various fluorescence assays. The observed results illustrate that BPA exposure potentiates/aggravates hypertension induced tissue abnormalities (renal fibrosis), oxidative stress (ROS generation), elevated angiotensin‐converting enzyme activity, malfunction of the antioxidant and tricarboxylic acid cycle enzymes, tissue lipid abnormalities and inflammatory factor expression (both messenger RNA and protein level of TNF‐α and IL‐6). Further, in vitro exposure of nM levels of BPA to primary kidney cells modulates oxidative stress (both superoxide and total ROS), mitochondrial physiology (reduced mitochondrial transmembrane potential—∆ψm) and lipid peroxidation in a dose dependent manner. In addition, angiotensin II induced ROS generation was aggravated further by BPA during coexposure in kidney cells. Therefore, during risk assessment, a precise investigation on BPA exposure in hypertensive (CVD vulnerable) populations is highly suggested.

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Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy

Cited by 55 publications

References 99 publications

Direct Renin Inhibitors in Arterial Hypertension Treatment

Direct Renin Inhibitors in Arterial Hypertension Treatment

The Bioequivalence Between Valsartan Oral Solution and Suspension Formulations Developed for Pediatric Use

Exposure to low dose of Bisphenol A (BPA) intensifies kidney oxidative stress, inflammatory factors expression and modulates Angiotensin II signaling under hypertensive milieu

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