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Hypertension Research : Official... Jun 2021Circadian fluctuation disorder of the intrarenal renin-angiotensin system (RAS) causes that of blood pressure (BP) and renal damage. In renal damage with an impaired...
Circadian rhythm of the intrarenal renin-angiotensin system is caused by glomerular filtration of liver-derived angiotensinogen depending on glomerular capillary pressure in adriamycin nephropathy rats.
Circadian fluctuation disorder of the intrarenal renin-angiotensin system (RAS) causes that of blood pressure (BP) and renal damage. In renal damage with an impaired glomerular filtration barrier, liver-derived angiotensinogen (AGT) filtered through damaged glomeruli regulates intrarenal RAS activity. Furthermore, glomerular permeability is more strongly affected by glomerular hypertension than by systemic hypertension. Thus, we aimed to clarify whether the circadian rhythm of intrarenal RAS activity is influenced by AGT filtered through damaged glomeruli due to glomerular capillary pressure. Rats with adriamycin nephropathy and an impaired glomerular filtration barrier were compared with control rats. In adriamycin nephropathy rats, olmesartan medoxomil (an angiotensin II type 1 receptor blocker) or hydralazine (a vasodilator) was administered, and the levels of intrarenal RAS components in the active and rest phases were evaluated. Moreover, the diameter ratio of afferent to efferent arterioles (A/E ratio), an indicator of glomerular capillary pressure, and the glomerular sieving coefficient (GSC) based on multiphoton microscopy in vivo imaging, which reflects glomerular permeability, were determined. Mild renal dysfunction was induced, and the systemic BP increased, resulting in increased A/E ratios in the adriamycin nephropathy rats compared with the control rats. Fluctuations in intrarenal RAS activity occurred in parallel with circadian fluctuations in glomerular capillary pressure, which disappeared with olmesartan treatment and were maintained with hydralazine treatment. Furthermore, the GSCs for AGT also showed similar changes. In conclusion, intrarenal RAS activity is influenced by the filtration of liver-derived AGT from damaged glomeruli due to circadian fluctuation disorder of the glomerular capillary pressure.
Topics: Angiotensinogen; Animals; Circadian Rhythm; Doxorubicin; Glomerular Filtration Rate; Hydralazine; Hypertension; Kidney Diseases; Liver; Rats; Renin-Angiotensin System
PubMed: 33558668
DOI: 10.1038/s41440-021-00620-6 -
Blood Pressure Aug 2020Most guidelines for treatment of hypertension in the setting of diabetes recommend a blood pressure (BP) target of <130/80 mmHg. However, uncertainty exists about the... (Randomized Controlled Trial)
Randomized Controlled Trial
Most guidelines for treatment of hypertension in the setting of diabetes recommend a blood pressure (BP) target of <130/80 mmHg. However, uncertainty exists about the extent, effectiveness and safety of lowering BP in diabetics. To expand the evidence on this issue, we analysed data from the Randomised Olmesartan and Diabetes MicroAlbuminuria Prevention (ROADMAP) study population. Substudy with blood pressure readings.: The response after initiation of therapy and adequacy of BP control across patients with different BP levels at baseline were analysed.: BP at randomisation was 136.2(15.3)/80.6(9.5) [mean (SD)] mmHg with a range of 87-213/37-123 mmHg. At 1 year, mean BP was 127 (11.9)/75 (8.1) mmHg and the overall control rate (<130/80 mmHg) exceeded 61% in this population. The mean reductions in systolic [-9.4 (15.4) mmHg] and diastolic BP [-5.4 (9.5) mmHg] were highly dependent on the BP stage at Visit 1. At 1 year, treatment decreased the prevalence of patients with baseline BP levels of >160/100 from 9 to 2%[[mean BP change -31 (15.7)/ -14 (9.8) mmHg]] and of 140-159/90-99 mmHg from 32 to 11% [[mean BP change -16(12.7)/ -8.9 (8.7) mmHg]], with corresponding increases in the prevalence of patients with baseline BP levels of 120-139/80-99 from 48 to 65% [[mean BP change -4.1 (10.6)/ -3.1 (7.8) mmHg]]and of <120/80 from 11 to 22% [[mean BP change +5.9 (11.8)/+2.5 (8.6) mmHg]]. These effects did not change significantly thereafter and were maintained throughout follow-up.: Blood pressure control is feasible in patients with diabetes without nephropathy, independent of baseline BP values. Asymmetric BP-lowering in the first year after starting therapy represents a true antihypertensive effect with sustainable shifts in BP severity.
Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Diabetes Mellitus; Double-Blind Method; Europe; Female; Humans; Hypertension; Male; Olmesartan Medoxomil; Time Factors; Treatment Outcome
PubMed: 32279529
DOI: 10.1080/08037051.2020.1750298 -
Gastroenterology Research Aug 2020Olmesartan is an angiotensin II receptor blocker (ARB) drug approved in 2002 for the treatment of hypertension. Since 2012, there have been reports of a rare adverse...
Olmesartan is an angiotensin II receptor blocker (ARB) drug approved in 2002 for the treatment of hypertension. Since 2012, there have been reports of a rare adverse effect suspected to be related to its use. The author presents a case of a 63-year-old female with refractory gastrointestinal (GI) symptoms including diarrhea with associated weight loss and severe electrolyte abnormalities necessitating hospitalization. An extensive inpatient evaluation ensued and was initially unremarkable. Esophagogastroduodenoscopy (EGD) discovered an endoscopically normal duodenum that was biopsied and notably revealed villous atrophy and intraepithelial lymphocytosis. Colonoscopy was normal appearing though biopsy findings were significant for nonspecific colitis. The endoscopy findings in the setting of the clinical presentation confirmed the diagnosis of olmesartan-associated enteropathy (OAE). Clinical improvement was noted after cessation of olmesartan and histological resolution was confirmed with repeat EGD post-discharge.
PubMed: 32864026
DOI: 10.14740/gr1301 -
Saudi Pharmaceutical Journal : SPJ :... Mar 2024This study was designed to assess both the quality and cost aspects of various branded and generic formulations of angiotensin receptor blockers, specifically...
This study was designed to assess both the quality and cost aspects of various branded and generic formulations of angiotensin receptor blockers, specifically Irbesartan, Losartan Potassium, Olmesartan Medoxomil, Telmisartan, and Valsartan. The collected samples underwent distinct quality evaluations using the methods outlined in different global Pharmacopoeias (British Pharmacopoeia/European Pharmacopoeia, Indian Pharmacopoeia and United States Pharmacopoeia). These drugs were characterized using Fourier-Transform Infrared Spectroscopy and Nuclear Magnetic Resonance techniques, while their quality and concentration were analysed using High Performance Liquid Chromatography. The release profile of the drugs was examined through dissolution testing. Additionally, a cost comparison analysis was carried out by determining the prevailing market prices of the drugs. The evaluated branded and generic angiotensin receptor blockers were found to meet the established standards for impurities, active drug content, and dissolution as set by these Pharmacopoeias, indicating their optimal quality. Notably, the generic drugs exhibited significantly lower costs compared to their branded counterparts. This study confirms that the quality of generic angiotensin receptor blockers is equivalent to that of their branded counterparts. Consequently, these findings support the practicality of utilizing generic drugs as a more economically sustainable and cost-effective approach to managing diseases, especially those of chronic nature.
PubMed: 38380162
DOI: 10.1016/j.jsps.2024.101985 -
Environmental Microbiology Reports Oct 2022Hexavalent chromium resistance and reduction mechanisms of microorganism provide a critical guidance for Cr(VI) bioremediation. However, related researches are limited...
Exploration on the Cr(VI) resistance mechanism of a novel thermophilic Cr(VI)-reducing bacteria Anoxybacillus flavithermus ABF1 isolated from Tengchong geothermal region, China.
Hexavalent chromium resistance and reduction mechanisms of microorganism provide a critical guidance for Cr(VI) bioremediation. However, related researches are limited in mesophiles and deficient for thermophiles. In this work, a novel alkaline Cr(VI)-reducing thermophile Anoxybacillus flavithermus ABF1 was isolated from geothermal region. The mechanisms of Cr(VI) resistance and reduction were investigated. The results demonstrated that A. flavithermus ABF1 could survive in a wide temperature range from 50°C to 70°C and in pH range of 7.0-9.0. Strain ABF1 showed excellent growth activity and Cr(VI) removal performance when initial Cr(VI) concentration was lower than 200 mg L . 93.71% of Cr(VI) was removed at initial concentration of 20 mg L after 72 h. The majority of Cr(VI) was found to be reduced extracellularly by enzymes secreted by cells. XPS and Raman analysis further manifested that Cr O was the product of Cr(VI) reduction. Moreover, the Cr(VI) transportation-related gene cysP and Cr(VI) reduction-related gene azoR of A. flavithermus ABF1 played key roles in inhibiting Cr(VI) entering cells and promoting extracellular Cr(VI) reduction respectively. This work provides novel insight into the mechanisms of Cr(VI) resistance and detoxication of thermophiles, which leads to a promising alternative strategy for heavy metal bioremediation in areas with elevated temperature.
Topics: Amlodipine Besylate, Olmesartan Medoxomil Drug Combination; Anoxybacillus; Bacteria; Biodegradation, Environmental; Chromium; Metals, Heavy; Oxidation-Reduction
PubMed: 35701897
DOI: 10.1111/1758-2229.13070 -
BMJ Case Reports Apr 2024This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman...
This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman who consumed an overdose of multiple medications: nifedipine, azelnidipine, amlodipine besylate, olmesartan medoxomil, telmisartan, esaxerenone and vildagliptin. She presented with haemodynamic instability, necessitating intubation. Despite stabilising haemodynamic parameters within 24 hours, she manifested escalating extremity oedema. At 52 hours after ingestion, mottled skin was observed, along with necrotic alterations in the swollen hands and compartment pressures exceeding 30 mm Hg in all extremities. ACS was diagnosed, leading to fasciotomies. The aetiology is postulated to be drug-induced angio-oedema, possibly intensified by the concurrent overdose of olmesartan medoxomil, telmisartan and vildagliptin, each of which has a risk of angio-oedema even at standard dosages. This scenario is a very rare case caused by drug-induced angio-oedema, which underscores the importance of vigilant monitoring to detect ACS in patients with progressing limb oedema.
Topics: Middle Aged; Female; Humans; Olmesartan Medoxomil; Telmisartan; Vildagliptin; Polypharmacy; Amlodipine; Drug Overdose; Angioedema; Tetrazoles; Antihypertensive Agents; Hypertension
PubMed: 38569737
DOI: 10.1136/bcr-2023-259485 -
Current Pain and Headache Reports Sep 2019Systematic review of angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARB) in the prophylactic treatment of adults with...
PURPOSE OF REVIEW
Systematic review of angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARB) in the prophylactic treatment of adults with migraine. To identify gaps in research and provide guidance for future clinical trials.
RECENT FINDINGS
A search was completed using PubMed, MEDLINE, Embase, and the Cochrane Library January 1, 1990 through December 31, 2017. The following are keywords used in the search: migraine, migraine prophylaxis/prevention, renin-angiotensin-aldosterone system, RAAS, ACE inhibitors, angiotensin-converting enzyme inhibitors: quinapril, perindopril, ramipril, captopril, enalapril, lisinopril, benazepril, fosinopril. Angiotensin receptor blockers, ARB, angiotensin II receptor antagonists: candesartan cilexetil, irbesartan, olmesartan, valsartan, losartan, azilsartan medoxomil, telmisartan, and eprosartan. The search included randomized controlled trials (RCT), systemic reviews and open-label studies of ACE inhibitors and ARB for the prevention of migraine attacks in adults 18-70 years old. Of 2461 retrieved articles, 18 included RCT, meta-analysis, systemic reviews, or guidelines published on ACE inhibitors or ARB in the prevention of migraine. Three RCT with telmisartan 80 mg, candesartan 16 mg, and enalapril 10 mg, and two open-label trials with lisinopril 5 mg and ramipril 5 mg found a high number of responders with greater than 50 % reduction in migraine attack frequency when compared to a 4-week baseline period. Candesartan was superior to placebo while telmisartan and enalapril were not. Lipophilic ACE inhibitors and ARBs can be effective prophylactic agents for reduction of migraine frequency in adults. Based on the limited number of published trials and small sample size, they are not recommended as first-line prophylactic agents. However, in populations with co-morbidities such as hypertension, they may be useful as first- or second-line prophylactics. Additional trials following the International Headache Society's guidelines on RCT are warranted.
Topics: Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Female; Humans; Male; Migraine Disorders
PubMed: 31515634
DOI: 10.1007/s11916-019-0823-8 -
Journal of Pharmaceutical and... Jan 2021Determination of azide as an impurity in medicinal products was performed for the following sartans with tetrazole functional group (synthesized with the use of azide...
A novel simple and precise method for the determination of azide impurity in sartans using headspace gas chromatography with two dissimilar capillary columns and two flame ionization detectors (HS-GC-FID/FID).
Determination of azide as an impurity in medicinal products was performed for the following sartans with tetrazole functional group (synthesized with the use of azide ion): candesartan, losartan, irbesartan, olmesartan medoxomil, and valsartan. This was achieved using headspace gas chromatography using a dual column/dual flame ionization detector (HS-GC-FID/FID). The method was linear in range, from 5.0-30.0 μg/g, with a coefficient of determination of >0.998 (R). The limit of quantification was 5.0 μg/g and the detection limit was 1.9 μg/g. The sample preparation procedure is fast and simple. The validation procedure was performed in accordance with International Conference on Harmonization (ICH) and Pharmacopeia guidelines. Moreover, besides the content of azide ions, trace quantities of residual solvents (methanol, ethanol, acetone, isopropanol) were found in the majority of sartan tablets.
Topics: Angiotensin II Type 1 Receptor Blockers; Azides; Chromatography, Gas; Flame Ionization; Methanol
PubMed: 33099116
DOI: 10.1016/j.jpba.2020.113671 -
European Journal of Pharmacology Aug 2022Diabetic nephropathy (DN) is one of the most serious consequences of diabetes and the most common reason for end-stage renal disease. The current study was set out to...
Diabetic nephropathy (DN) is one of the most serious consequences of diabetes and the most common reason for end-stage renal disease. The current study was set out to investigate the ability of olmesartan medoxomil (OM) to treat DN by evaluating the reno-protective effects of this drug on fat/fructose/streptozotocin (F/Fr/STZ)-induced diabetic rat model. This model was induced by feeding rats high F/Fr diet for 7 weeks followed by injection of a single sub-diabetogenic dose of STZ (35mg/kg; i.p). The F/Fr/STZ-induced diabetic rats were orally treated with either OM (10 mg/kg) or pioglitazone (10 mg/kg); as a standard drug daily for four consecutive weeks. F/Fr/STZ-induced diabetic rats propagated inflammatory, oxidative, and fibrotic events. OM was able to oppose the injurious effects of diabetes; it significantly reduced the elevated levels of advanced glycated end products (AGEs) and downregulated PKC gene expression, therefore, indicating its antioxidant capacity evidenced by mitigation in GSH, MDA renal content. Moreover, OM impaired the inflammatory cascade by suppressing the elevated level of renal TLR4 as well as diminished the inflammatory profibrotic cytokine TGF-β1. Additionally, OM was able to turn off the MAPK cascade mediated by an upsurge in renal angiotensin 1-7 content and decrease the level of renal tubular injury marker, KIM-1. Furthermore, OM enhanced the autophagic activity pathway by upregulating of gene expression of SIRT-1. The histopathological examination confirmed these results. Finally, OM protected against type 2 diabetes-related nephropathy complications by altering inflammatory pathways, oxidative, fibrotic, and autophagic processes triggered by renal glucose overload. This study shows that OM has a reno-protective effect against DN in rats by inhibiting the AGE/PKC, TLR4/P38-MAPK, and SIRT-1 autophagic signaling pathways.
Topics: Animals; Diabetes Complications; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Fructose; Imidazoles; Kidney; Oxidative Stress; Rats; Signal Transduction; Sirtuins; Streptozocin; Tetrazoles; Toll-Like Receptor 4; p38 Mitogen-Activated Protein Kinases
PubMed: 35752350
DOI: 10.1016/j.ejphar.2022.175117 -
Digestive and Liver Disease : Official... Nov 2021
Topics: Angiotensin II Type 1 Receptor Blockers; Collagenous Sprue; Endoscopy, Digestive System; Female; Humans; Olmesartan Medoxomil
PubMed: 34219045
DOI: 10.1016/j.dld.2021.06.010