The capacity of renin-angiotensin system (RAS) inhibitors to delay progression of diabetic nephropathy depends on the time at which therapy is started. A multimodal intervention is required to afford renoprotection in overt diabetic nephropathy. Here we assessed the effects of maximal RAS inhibition by angiotensin-converting enzyme (ACE) inhibitor plus angiotensin II type 1 receptor blocker (ARB) in combination with statin in rats with overt diabetic nephropathy. Uninephrectomized rats made diabetic by streptozotocin were orally treated from 4 (when proteinuria and renal lesions had developed) to 8 mo with vehicle, lisinopril plus candesartan, lisinopril plus candesartan plus rosuvastatin, or rosuvastatin alone. Systolic blood pressure increased in diabetic rats and was significantly lowered by combined therapies. Dual RAS blockade significantly reduced proteinuria compared with vehicle. Addition of statin further lowered proteinuria to control levels. Glomerulosclerosis was ameliorated by RAS inhibitors or statin, and regression was achieved by the addition of statin. Loss of podocytes of diabetic rats was limited by ACE inhibitor plus ARB while normalized by the three drugs. Defective nephrin expression of diabetes was increased by dual RAS blockade or statin and restored by the triple therapy. Tubular damage, interstitial inflammation, and expression of the fibrotic markers transforming growth factor (TGF)-β1 and phosphorylated Smad 2/3 in tubuli were significantly reduced by the triple regimen. These data suggest a strategy to target proteinuria to try to achieve regression of renal disease in diabetic patients who do not fully benefit from RAS inhibition alone.
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http://dx.doi.org/10.1152/ajprenal.00045.2010 | DOI Listing |
Br J Anaesth
December 2024
Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK. Electronic address:
Background: Hypertension therapy in older adults is often suboptimal, in part because of inadequate suppression of the renin-angiotensin-aldosterone system (RAAS). We hypothesised that distinct endotypes of RAAS activation before noncardiac surgery are associated with increased risk of myocardial injury.
Methods: This was a prespecified exploratory analysis of a multicentre randomised controlled trial (ISRCTN17251494) which randomised patients ≥60 yr old undergoing elective noncardiac surgery to either continue or stop RAAS inhibitors (determined by pharmacokinetic profiles).
Clin Exp Med
December 2024
Department of Medicine, King's College Hospital NHS Foundation Trust, London, UK.
Background: Inhibitors of the renin-angiotensin-aldosterone system (RAAS), such as ACE inhibitors (ACEi), angiotensin-II receptor blockers and mineralocorticoid receptor antagonists, reduce morbidity and mortality in hypertension, congestive heart failure and chronic kidney disease. However, their use can lead to hyperkalaemia. We examined the proportions of RAAS inhibitor (RAASi) reduction or withdrawal, across GFR strata, following hospitalisation and the effect on patient mortality.
View Article and Find Full Text PDFEur J Med Chem
December 2024
Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China. Electronic address:
The application of therapeutic agents for cardiopathy has brought about significant advancements in the treatment of cardiovascular diseases. The intervention of small-molecule drugs has led to substantial reductions in morbidity and mortality rates, along with decreased utilization of healthcare resources. However, current treatment modalities do not exhibit uniform efficacy across all patients, and the emergence of drug resistance poses a significant challenge to further therapeutic efforts.
View Article and Find Full Text PDFDaru
December 2024
Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
Background: High-performance liquid chromatography (HPLC) has emerged as a highly sensitive and versatile analytical technique for quantifying antihypertensive drugs, such as Captopril (CAP). This study focused on the optimization and validation of an HPLC method for quantifying CAP in an in vitro hydrogel permeability test.
Objectives: The main objective of this study was to develop and validate an HPLC method for quantifying CAP in an in vitro hydrogel permeability test.
Eur J Clin Pharmacol
December 2024
Faculty of Pharmacy, Université de Montréal, 2940 Chemin de Polytechnique, Montreal, Quebec, H3T 1J4, Canada.
Background: Women are underrepresented in drug development trials and there is no sex-tailored drug regimen for most medications. It has been repeatedly shown that women have more adverse drug reactions than men for several medications. These differences could be explained by higher dose-adjusted drug concentrations in women.
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