ArticleBritish journal of pharmacology2005
Effects of statins on vascular function of endothelin-1.
Article in British journal of pharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03896217 (A Double-blind, Randomised, Placebo-controlled Single-site Study of High Dose Simvastatin Treatment for Secondary Progressive Multiple Sclerosis), which is not on this map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Double-blind, Randomised, Placebo-controlled Single-site Study of High Dose Simvastatin Treatment for Secondary Progressive Multiple Sclerosis: Impact on Vascular Perfusion and Oxidative Damage
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pre-morbid statin use and mortality in trauma: a systematic review and meta-analysis.Langenbeck's archives of surgery · 2026Pooled it
- Could Endothelin-1 Be a Promising Neurohormonal Biomarker in Acute Heart Failure?Diagnostics (Basel, Switzerland) · 2023Review
- Endothelin-1 is associated with mortality that can be attenuated with high intensity statin therapy in patients with stable coronary artery disease.Communications medicine · 2023Article
- New insights on mode of action of vasorelaxant activity of simvastatin.Inflammopharmacology · 2023Article
- Review
- Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Ggps1 deficiency in the uterus results in dystocia by disrupting uterine contraction.Journal of molecular cell biology · 2021Article
- Emerging antenatal therapies for congenital diaphragmatic hernia-induced pulmonary hypertension in preclinical models.Pediatric research · 2021Review
- Repurposing simvastatin as a therapy for preterm labor: evidence from preclinical models.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Article
- Three-year change in endothelin-1 and markers of vascular remodelling in a bi-ethnic South African cohort: the SABPA study.Journal of human hypertension · 2017Article
- Severe depressive symptoms are associated with elevated endothelin-1 in younger patients with acute coronary syndrome.Journal of psychosomatic research · 2014Article
- Statins and vein graft failure in coronary bypass surgery.Current opinion in pharmacology · 2012Review
- Depression predicts elevated endothelin-1 in patients with coronary artery disease.Psychosomatic medicine · 2011Article
- Tendency to angry rumination predicts stress-provoked endothelin-1 increase in patients with coronary artery disease.Psychosomatic medicine · 2010Article
- Role of statins in cerebral vasospasm.Acta neurochirurgica. Supplement · 2008Article
- A novel mechanism of action for statins against diabetes-induced oxidative stress.Diabetologia · 2007Article
- Molecular programming of endothelin-1 in HIV-infected brain: role of Tat in up-regulation of ET-1 and its inhibition by statins.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2007Article
- The future of endothelin-receptor antagonism as treatment for systemic hypertension.Current hypertension reports · 2006Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. Although statins have been reported to inhibit the prepro-endothelin-1 (ET-1) gene transcription in endothelial cells, their effects on the vascular function of ET-1 have not been explored. We, therefore, examined the effects of statins on contraction and DNA synthesis mediated by ET-1 in vascular smooth muscle. The effects of statins on contraction induced by ET-1 were compared to those mediated by noradrenaline (NA) and KCl. 2. Simvastatin (SV) induced a concentration-dependent relaxation of tonic contraction mediated by ET-1 (10 nM) (IC50 value of 1.3 microM). The relaxation was also observed in rings precontracted with NA (0.1 microM) and KCl (60 mM). In contrast, pravastatin did not have any effect on the contractions. 3. Endothelial denudation or pretreatment with L-NAME did not prevent the relaxation, but did reduce the relaxant activity of SV. 4. SV prevented Rho activation caused by ET-1 and KCl in aortic homogenates, as assessed by a Rho pulldown assay. 5. The Rho kinase inhibitor HA-1077 mimicked the effects of SV on tonic contractions induced by ET-1, NA and KCl. 6. Pretreatment with the Kv channels inhibitor, 4-aminopyridine, attenuated the ability of SV to relax contractions mediated by ET-1 and NA. 7. In quiescent VSM cells, SV significantly inhibited DNA synthesis and Rho translocation stimulated by ET-1, as assessed by [3H]thymidine incorporation and Western blot, respectively. 8. Inhibition of Rho geranylgeranylation by GGTI-297, or treatment with HA-1077, mimicked the effects of SV on DNA synthesis stimulated by ET-1. 9. The results show that the statin potently inhibits both ET-1-mediated contraction and DNA synthesis via multiple mechanisms. Clinical benefits of statins may result, in part, from their effects on vascular function of ET-1.
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