- Angiotensin-converting enzyme inhibitor reduces scar formation by inhibiting both canonical and noncanonical TGF-β1 pathways. [Journal Article]
- SRSci Rep 2018 Feb 20; 8(1):3332
- Angiotensin-converting enzyme inhibitors (ACEIs) can improve the fibrotic processes in many internal organs. Recent studies have shown a relationship between ACEI with cutaneous scar formation, altho...
Angiotensin-converting enzyme inhibitors (ACEIs) can improve the fibrotic processes in many internal organs. Recent studies have shown a relationship between ACEI with cutaneous scar formation, although it has not been confirmed, and the underlying mechanism is unclear. In this study, we cultured mouse NIH 3T3 fibroblasts with different concentrations of ACEI. We measured cell proliferation with a Cell Counting Kit-8 and collagen expression with a Sirius Red Collagen Detection Kit. Flow cytometry and western blotting were used to detect transforming growth factor β1 (TGF-β1) signaling. We also confirmed the potential antifibrotic activity of ACEI in a rat scar model. ACEI reduced fibroblast proliferation, suppressed collagen and TGF-β1 expression, and downregulated the phosphorylation of SMAD2/3 and TAK1, both in vitro and in vivo. A microscopic examination showed that rat scars treated with ramipril or losartan were not only narrower than in the controls, but also displayed enhanced re-epithelialization and neovascularization, and the formation of organized granulation tissue. These data indicate that ACEI inhibits scar formation by suppressing both TGF-β1/SMAD2/3 and TGF-β1/TAK1 pathways, and may have clinical utility in the future.
- Fixed-dose vs free-dose combinations for the management of hypertension-An analysis of 81 958 patients. [Journal Article]
- JCJ Clin Hypertens (Greenwich) 2018 Feb 19
- Fixed-dose combinations (FDC) have been developed to reduce the pill burden for hypertensive patients. Data on fixed-dose or free-dose (freeDC) ramipril/amlodipine (R/A) or candesartan/amlodipine (C/...
Fixed-dose combinations (FDC) have been developed to reduce the pill burden for hypertensive patients. Data on fixed-dose or free-dose (freeDC) ramipril/amlodipine (R/A) or candesartan/amlodipine (C/A) combination treatment initiation were assessed. 71 463 patients were prescribed R/A and 10 495 C/A. For both R/A and C/A, FDC patients were younger (both P < .001) and less comorbid. Prior MI (OR: 0.61 and 0.60), prior stroke (OR: 0.68 and 0.70) and CHD (OR: 0.68 and 0.64) were negatively associated with FDC use, whereas hyperlipidemia was positively associated (OR: 1.26 and 1.19). Use of antihypertensive comedication (OR: 0.78; OR: 0.55) and treatment discontinuation within 12 months (HR: 0.65 and 0.82) were less likely in FDC patients, who also showed superior adherence (mean MPR; both P < .001). Cost of the combination was higher for FDCs (both P < .001). FDCs improve persistence and adherence, although they are more commonly prescribed in patients with less cardiovascular disease.
- Impact of renin-angiotensin system inhibitors on clinical outcomes and ventricular remodelling after transcatheter aortic valve implantation: rationale and design of the RASTAVI randomised multicentre study. [Journal Article]
- BOBMJ Open 2018 02 13; 8(2):e020255
- Transcatheter aortic valve implantation (TAVI) as a treatment in severe aortic stenosis (AS) is an excellent alternative to conventional surgical replacement. However, long-term outcomes are not beni...
Transcatheter aortic valve implantation (TAVI) as a treatment in severe aortic stenosis (AS) is an excellent alternative to conventional surgical replacement. However, long-term outcomes are not benign. Renin-angiotensin system (RAS) blockade has shown benefit in terms of adverse remodelling in severe AS and after surgical replacement.
- The win ratio approach did not alter study conclusions and may mitigate concerns regarding unequal composite endpoints in kidney transplant trials. [Journal Article]
- JCJ Clin Epidemiol 2018 Feb 08
- CONCLUSIONS: The win ratio approach produced results similar to the original time-to-event analysis. Using this approach would not alter the conclusion of the original trial and lessens concerns associated with composite components of unequal clinical importance.
- [Gallop in the Routineergometrie: Only Chore or Diagnostic Challenge?] [Journal Article]
- DMDtsch Med Wochenschr 2018; 143(3):193-197
- CONCLUSIONS: Most patients have cardiac insufficiency, rhythmic symptoms, or thrombi formation in the noncompact portions of the left ventricular wall. Ventricular tachycardias are frequent and sudden cardiac death is the leading cause of death. Arrythmias are accessible to medication or ablation treatment. Endurance sports lead to favorable adaptations of the cardiovascular system in spite of increased risk of sudden cardiac death. The example shows that asymptomatic boundary findings also exist. Whether a sporting activity has a protective influence must be further investigated.
- The effects of angiotensin converting enzyme inhibition and alpha 1-adrenergic receptor blockade on inflammation and hemostasis in human hypertension. [Journal Article]
- JCJ Cardiovasc Pharmacol 2018 Jan 30
- Drugs blocking the renin-angiotensin-aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We examined the ...
Drugs blocking the renin-angiotensin-aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We examined the contribution of the angiotensin converting enzyme inhibitor ramipril and the alpha 1-adrenergic receptor blocker doxazosin on blood pressure and on markers of inflammation and hemostasis in 59 individuals with mild-to-moderate hypertension randomized to receive double blind ramipril 10 mg od or doxazosin 8 mg od for 12 weeks. Inflammatory markers (interleukin-6, soluble interleukin-6 receptor, interleukin-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, and C-reactive protein) and hemostasis (plasminogen activator inhibitor-1 activity, tissue plasminogen activator antigen, thrombin-antithrombin complex, and thrombin generation by calibrated automated thrombogram) were assessed. Treatment reduced blood pressure in both groups. Thrombin-antithrombin complex decreased by treatment, and this was dependent on a reduction in thrombin-antithrombin complex in the ramipril group alone. There were no changes in plasminogen activator inhibitor-1 activity, while tissue plasminogen activator antigen increased by ramipril and decreased by doxazosin. Only minor changes were observed in systemic inflammation by treatment. Treatment with ramipril appears to reduce thrombin generation beyond effects on reducing blood pressure. Drugs blocking the renin-angiotensin-aldosterone system may reduce atherothrombotic complications beyond their effects to reduce blood pressure.
- Angiotensin-(1-7) Inhibits Thrombin-Induced Endothelial Phenotypic Changes and Reactive Oxygen Species Production via NADPH Oxidase 5 Downregulation. [Journal Article]
- FPFront Physiol 2017; 8:994
- CONCLUSIONS: Angiotensin-(1-7) prevents actin cytoskeleton derangement, monocyte adhesion, and migration impairment induced by thrombin via downregulation of ROS production. In addition, thrombin-induced Nox5 expression is involved in the production of ROS, and angiotensin-(1-7) decreases ROS through its inhibitory effect on Nox5 expression.
- Clinical efficacy of African traditional medicines in hypertension: A randomized controlled trial with Combretum micranthum and Hibiscus sabdariffa. [Journal Article]
- JHJ Hum Hypertens 2017; 32(1):75-81
- Medicinal plants are widely used as a first-line therapy for hypertension, often without comparative clinical data. A prospective, randomized controlled trial was conducted to assess efficacy of Comb...
Medicinal plants are widely used as a first-line therapy for hypertension, often without comparative clinical data. A prospective, randomized controlled trial was conducted to assess efficacy of Combretum micranthum (kinkeliba) and Hibiscus sabdariffa (bissap), in the galenic form of capsules of plant powder, on blood pressure in adult patients with non-complicated hypertension ( > 140/90 mm Hg). One hundred and twenty five patients were randomly allocated into group 1 (kinkeliba leaves 190 mg × 2/day), or group 2 (bissap calyx 320 mg × 2/day), or group 3 (ramipril 5 mg /day) during four consecutive weeks. Blood and urinary samples were collected on day 0 and 28 while patients' blood pressure was measured weekly. In all three groups SBP and DBP decreased over 3 weeks of treatment (P < 0.001). For SBP, mean decrease was higher with ramipril (-16.7 ± 8.4 mm Hg) than with kinkeliba (-12.2 ± 6.6 mm Hg, P = 0.016) and bissap (-11.2 ± 3.3 mm Hg, P = 0.001). For DBP, mean decrease with ramipril (-6.7 ± 3.6 mm Hg) was more important than with kinkeliba (-5.0 ± 3.0 mm Hg, P = 0.011) but not statistically different to bissap group (-6.0 ± 4.7 mm Hg, P = 0.271). A significant natriuretic effect was observed in the kinkeliba and bissap groups but not in patients under ramipril treatment. At the end of the four weeks, 39% [95% CI: 25.7-54.3] of patients in the ramipril group, 37% [95% CI: 23.6-51.9] of patients in the kinkeliba group and 21% [95% CI: 11.7-35.9] of those taking bissap had normalized their BP.
- Antihypertensive treatment prescription in pediatric dialysis patients in Poland: A comparison between two nationwide studies 2003/2004-2013. [Journal Article]
- ACAdv Clin Exp Med 2017; 26(8):1263-1268
- CONCLUSIONS: Antihypertensive treatment in dialyzed children did not change significantly during the last decade with regard to the groups of drugs being used. Despite a wider feasibility of antihypertensive substances, the effectiveness of this therapy was still unsatisfactory.
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- The effects of single and combined application of ramipril and losartan on renal structure and function in hypertensive rats. [Journal Article]
- CEClin Exp Hypertens 2017 Dec 19; :1-7
- The objective of the present study was to investigate the effects of single and combined administration of ramipril and losartan on renal structure and function in spontaneously hypertensive rats (SH...
The objective of the present study was to investigate the effects of single and combined administration of ramipril and losartan on renal structure and function in spontaneously hypertensive rats (SHRs). Thirty-two 9-week-old SHRs and eight Wistar-Kyoto (WKY) rats were randomly divided into five groups: the WKY control group, the SHR control group, the SHR-ramipril group, the SHR-losartan group, and the SHR-combined mediation group. The rat body weight, SBP, heart rate, and urinary albumin excretion rate (UAER) were measured. (1) The SBP was reduced to the normal level in all groups of rats except for the SHR control group. Combined administration of ramipril and losartan can be reduced to the normal level earlier than single (P < 0.01). (2) The SHR-ramipril group and the SHR-losartan group still experienced a higher UAER than that in the WKY control group (P < 0.01). (3) The renal mass/BW ratio was decreased in the SHR-ramipril group, SHR-losartan group, and SHR-combined medication group compared to that in the SHR control group (P < 0.01). (4) Compared with the SHR control group, the SHR-ramipril group, the SHR-losartan group, and the SHR-combined medication group had a lower percentage of the IOD of glomerular collagen relative to the glomerular area (P < 0.01). (5) The reduction in tubulointerstitial injury score was more significant in the SHR-combined medication group than in the SHR-ramipril group and the SHR-losartan group (P < 0.01). The combination of ramipril and losartan is superior to either single drug in reducing the UAER, resisting glomerular collagen deposition, and protecting renal tubular structure.