ArticleJournal of molecular and cellular cardiology2015
Nifedipine attenuation of abdominal aortic aneurysm in hypertensive and non-hypertensive mice: Mechanisms and implications.
Article in Journal of molecular and cellular cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- CALHM5 deficiency alleviates aortic aneurysm by regulating smooth muscle calcium homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Attenuation of advanced atherosclerosis and aortic aneurysm in hph-1/apoE DKO mice by folic acid and DHFR overexpression.Frontiers in physiology · 2026Article
- Therapeutic Strategies for Abdominal Aortic Aneurysm: A Comprehensive Systematic Review.Journal of cardiovascular development and disease · 2025Review
- L-type calcium channel blockade worsens glucose tolerance and β-cell function in C57BL6/J mice exposed to intermittent hypoxia.American journal of physiology. Endocrinology and metabolism · 2025Article
- Taohong Siwu Decoction alleviates high salt-induced calcium overload and ferroptosis in vascular endothelial cells in hypertension by regulating ATF4.Frontiers in nutrition · 2025Article
- Reversal of Pulmonary Hypertension in a Human-Like Model: Therapeutic Targeting of Endothelial DHFR.Circulation research · 2024Article
- Identification of abdominal aortic aneurysm subtypes based on mechanosensitive genes.PloS one · 2024Article
- Role of sonic hedgehog signaling pathway in the regulation of ion channels: focus on its association with cardio-cerebrovascular diseases.Journal of physiology and biochemistry · 2023Review
- Evaluation of Cartilage Integrity Following Administration of Oral and Intraarticular Nifedipine in a Murine Model of Osteoarthritis.Biomedicines · 2023Article
- Novel pharmacological approaches in abdominal aortic aneurysm.Clinical science (London, England : 1979) · 2023Review
- Increased plasma renin by vasodilators promotes the progression of abdominal aortic aneurysm.Frontiers in pharmacology · 2023Article
- Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication.Redox biology · 2022Article
- Diagnostic and predictive values of circulating tetrahydrobiopterin levels as a novel biomarker in patients with thoracic and abdominal aortic aneurysms.Redox biology · 2022Article
- Twenty Years of Studying AngII (Angiotensin II)-Induced Abdominal Aortic Pathologies in Mice: Continuing Questions and Challenges to Provide Insight Into the Human Disease.Arteriosclerosis, thrombosis, and vascular biology · 2022Review
- Targeting MicroRNA-192-5p, a Downstream Effector of NOXs (NADPH Oxidases), Reverses Endothelial DHFR (Dihydrofolate Reductase) Deficiency to Attenuate Abdominal Aortic Aneurysm Formation.Hypertension (Dallas, Tex. : 1979) · 2021Article
- Targeting mitochondrial fission as a potential therapeutic for abdominal aortic aneurysm.Cardiovascular research · 2021Article
- Potential Roles of Endoplasmic Reticulum Stress and Cellular Proteins Implicated in Diabesity.Oxidative medicine and cellular longevity · 2021Review
- Knockout of dihydrofolate reductase in mice induces hypertension and abdominal aortic aneurysm via mitochondrial dysfunction.Redox biology · 2019Article
- Pharmacologic Management of Aneurysms.Circulation research · 2019Review
- Calcium in Vascular Smooth Muscle Cell Elasticity and Adhesion: Novel Insights Into the Mechanism of Action.Frontiers in physiology · 2019Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
Rupture of abdominal aortic aneurysm (AAA) is a lethal event. No oral medicine has been available to prevent or treat AAA. We have recently identified a novel mechanism of eNOS uncoupling by which AAA develops, in angiotensin II (Ang II) infused hyperphenylalaninemia 1 (hph-1) mice. Using this unique model we investigated effects on AAA formation of the L-type calcium channel blocker nifedipine, in view of the unclear relationship between hypertension and AAA, and unclear mechanisms of aneurysm protective effects of some blood pressure lowering drugs. Six-month old hph-1 mice were infused with Ang II (0.7 mg/kg/day) for 2 weeks, and fed nifedipine chow at two different doses (5 and 20 mg/kg/day). While the high dose of nifedipine reduced blood pressure, the lower dose had no effect. Interestingly, the incidence rate of AAA dropped from 71% to 7 and 12.5% for low and high dose nifedipine, respectively. Expansion of abdominal aorta, determined by ultrasound imaging, was abolished by both doses of nifedipine, which recoupled eNOS completely to improve NO bioavailability. Both also abrogated aortic superoxide production. Of note, Ang II activation of NADPH oxidase in vascular smooth muscle cells and endothelial cells, known to uncouple eNOS, was also attenuated by nifedipine. Although low dose was a sub-pressor while the high dose reduced blood pressure via inhibition of calcium channels, both doses were highly effective in preventing AAA by preserving eNOS coupling activity to eliminate sustained oxidative stress from uncoupled eNOS. These data demonstrate that oral treatment of nifedipine is highly effective in preserving eNOS function to attenuate AAA formation. Nifedipine may be used for AAA prevention either at low dose in AAA risk group, or at high dose in patients with co-existing hypertension.
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