Background: Activation of angiotensin (ANG) II type 1 receptors (AT1R) promotes vasoconstriction, inflammation, and renal dysfunction. In this study, we addressed the ability of azilsartan (AZL), a new AT1R antagonist, to modulate levels of plasma ANG-(1-7) and renal epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE).
Methods: Sprague-Dawley rats were infused with ANG II (125 ng/min) or vehicle (VEH). AZL (3 mg/kg/day) or VEH was administered starting 1 day prior to ANG II or VEH infusion. On day 10, plasma was obtained for measurement of ANG-(1-7) and kidneys for isolation of microvessels for EET and 20-HETE determination and histological evaluation.
Results: Mean 24-hour blood pressure (BP) was not different between VEH and AZL treatment groups, whereas the BP elevation with ANG II infusion (121 ± 5 mm Hg) was completely normalized with AZL cotreatment (86 ± 3 mm Hg). The ANG II-induced renal damage was attenuated and cardiac hypertrophy prevented with AZL cotreatment. Plasma ANG-(1-7) levels (pg/ml) were increased with AZL treatment (219 ± 22) and AZL + ANG II infusion (264 ± 93) compared to VEH controls (74.62 ± 8). AZL treatment increased the ratio of EETs to their dihydroxyeicosatrienoic acid (DHET) metabolites and reduced 20-HETE levels.
Conclusions: Treatment with AZL completely antagonized the elevation of BP induced by ANG II, prevented cardiac hypertrophy, attenuated renal damage, and increased ANG-(1-7) and EET/DHET ratio while diminishing 20-HETE levels. Increased ANG-(1-7) and EETs levels may emerge as novel therapeutic mechanisms contributing to the antihypertensive and antihypertrophic actions of AZL treatment and their relative role compared to AT1R blockade may depend on the etiology of the hypertension.
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http://dx.doi.org/10.1093/ajh/hpu201 | DOI Listing |
J Diabetes Metab Disord
June 2025
Department of Medicine, Gandhi Ward, King George's Medical University, Lucknow, India.
Purpose: Type 2 diabetes mellitus and hypertension frequently coexist, increasing the risk of cardiovascular and renal complications. Urinary Albumin Creatinine Ratio (UACR) serves as a crucial predictor of these outcomes. While renin-angiotensin system inhibitors are often initial therapy, evidence suggests a potential role for Azelnidipine, a non-dihydropyridine calcium channel blocker, in reducing UACR, especially in cases of persistent proteinuria despite optimal therapy.
View Article and Find Full Text PDFJ Neurooncol
November 2024
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Purpose: Treatment response assessment for gliomas currently uses changes in tumour size as measured with T- and T-weighted MRI. However, changes in tumour size may occur many weeks after therapy completion and are confounded by radiation treatment effects. Advanced MRI techniques sensitive to tumour physiology may provide complementary information to evaluate tumour response at early timepoints during therapy.
View Article and Find Full Text PDFAdv Ther
December 2024
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Introduction: A systematic literature review and network meta-analysis was conducted on azilsartan medoxomil (AZL-M) versus other antihypertensive drugs' efficacy in hypertensive patients.
Methods: The search utilized English platforms, from January 2000 until December 2023, resulting in 10,380 articles being screened. Screening criteria included hypertension (mild or moderate); first-line treatment and washout periods; studies (monotherapy) with AZL-M, angiotensin type II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitor (ARNIs), beta-blockers, calcium channel blockers (CCBs), and diuretics, either as intervention or comparator; and antihypertension efficacy as an outcome measure.
Front Cardiovasc Med
July 2024
Department of Pharmacy, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Background: Angiotensin II receptor blockers (ARBs) are utilized for the management of hypertension and diabetes. Previous meta-analyses suggested that azilsartan medoxomil (AZL-M) improved blood pressure (BP) reduction, but there were no safety findings or suggestions for patients with hypertension or diabetes.
Methods: We performed an efficacy and safety meta-analysis of randomized controlled trials (RCTs) evaluating AZL-M therapy for reducing BP in patients with hypertension.
Arthroscopy
June 2024
Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York, U.S.A.; Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, New York, U.S.A.
Purpose: To provide a proof-of-concept analysis of the appropriateness and performance of ChatGPT-4 to triage, synthesize differential diagnoses, and generate treatment plans concerning common presentations of knee pain.
Methods: Twenty knee complaints warranting triage and expanded scenarios were input into ChatGPT-4, with memory cleared prior to each new input to mitigate bias. For the 10 triage complaints, ChatGPT-4 was asked to generate a differential diagnosis that was graded for accuracy and suitability in comparison to a differential created by 2 orthopaedic sports medicine physicians.
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