Print Email Facebook Twitter No effects of atorvastatin (10 mg/d or 80 mg/d) on nitric oxide, prostacyclin, thromboxane and oxidative stress in type 2 diabetes mellitus patients of the DALI study Title No effects of atorvastatin (10 mg/d or 80 mg/d) on nitric oxide, prostacyclin, thromboxane and oxidative stress in type 2 diabetes mellitus patients of the DALI study Author Tsikas, D. Pham, V.V. Suchy, M.T. van de Ree, M.A. Huisman, M.V. Frölich, J.C. Princen, H.M.G. Publication year 2015 Abstract The present study describes the effects of atorvastatin on whole body synthesis of nitric oxide (NO), prostacyclin (PGI2), and thromboxane A2 (TxA2), on oxidative stress and nitrite/nitrate-related renal carbonic anhydrase (CA) activity in patients with type 2 diabetes mellitus (T2DM). A double-blind, randomized, placebo-controlled parallel-group trial (the DALI study group) on 217 patients with T2DM and dyslipidemia was performed. Urinary samples were collected before and after administration of a standard dose (10 mg/d, n = 73), a maximal dose atorvastatin (80 mg/d, n = 72) or placebo (n = 72) for 30 weeks. Urinary nitrite and nitrate were measured to assess whole body NO synthesis. The urinary molar ratio of nitrate to nitrite (UNOxR) served as a measure of renal CA activity. Free radical- and cyclooxygenase (COX)-catalyzed lipid peroxidation was estimated by measuring urinary 8-iso-prostaglandin F2α (8-iso-PGF2α). In subgroups, systemic PGI2 and TxA2 synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-6-keto-prostaglandin F1α and 2,3-dinor-thromboxane B2, respectively. All biochemical parameters were measured by GC-MS and GC-MS/MS methods. T2DM patients had elevated levels of nitrate, nitrite, UNOxR, and 8-iso-PGF2α compared to healthy non-diabetic and normolipidemic subjects. Thirty-week treatment with atorvastatin (10 or 80 mg/d) did not significantly alter NO, PGI2, TxA2 and 8-iso-PGF2α synthesis and did not improve the renal reabsorption of nitrite which is considered an important reservoir of NO. Our study suggests that atorvastatin (10 or 80 mg/d) does not provide cardiovascular benefit beyond its cholesterol lowering effect in patients with T2DM. © 2015 Elsevier Ltd. All rights reserved. Subject LifeMHR - Metabolic Health ResearchELSS - Earth, Life and Social SciencesBiomedical InnovationBiologyHealthy Living8-iso-Prostaglandin F2αCarbonic anhydraseCardiovascular diseaseDiabetes mellitus type 2Nitric oxideOxidative stressProstacyclinStatinsThromboxane2,3 dinor 6 oxoprostaglandin F1 alpha2,3 dinorthromboxane B28 isoprostaglandin F2 alphaAtorvastatinCarbonate dehydrataseCholesterolNitrateNitric oxideNitritePlaceboProstacyclinProstaglandin synthaseThromboxaneThromboxane A2AdultAgedAntioxidant activityBiosynthesisCholesterol metabolismControlled studyDose responseDouble blind procedureDrug effectDrug treatment failureDyslipidemiaFemaleHeart protectionLipid peroxidationLipolysisMajor clinical studyMaleMass fragmentographyMiddle agedNon insulin dependent diabetes mellitusOxidative stressRandomized controlled trialTandem mass spectrometryTreatment durationUrine level To reference this document use: http://resolver.tudelft.nl/uuid:7add2b5f-40bc-4fa5-b641-ec348ffdb1e3 DOI https://doi.org/10.1016/j.phrs.2015.01.004 TNO identifier 524120 ISSN 1043-6618 Source Pharmacological Research, 94, 1-8 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.