TY - JOUR
T1 - 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
AU - Tsikas, Dimitrios
AU - Pham, Vu Vi
AU - Suchy, Maria-Theresia
AU - van de Ree, Marcel A.
AU - Huisman, Menno V.
AU - Frölich, Jürgen C.
AU - Princen, Hans M. G.
AU - AUTHOR GROUP
AU - Berk-Planken, I.
AU - Hoogerbrugge, N.
AU - Jansen, H.
AU - Princen, H. M. G.
AU - Huisman, M. V.
AU - van de Ree, M. A.
AU - Stolk, R. P.
AU - van Venrooij, F. V.
AU - Banga, J. D.
AU - Dallinga-Thie, G.
PY - 2015
Y1 - 2015
N2 - The present study describes the effects of atorvastatin on whole body synthesis of nitric oxide (NO), prostacyclin (PGI(2)), and thromboxane A(2) (TxA(2)), 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 (U-NoxR) served as a measure of renal CA activity. Free radical- and cyclooxygenase (COX)-catalyzed lipid peroxidation was estimated by measuring urinary 8-iso-prostaglandin F-2 alpha (8-iso-PGF(2 alpha)). In subgroups, systemic PGI(2) and TxA(2) synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-6-keto-prostaglandin F-1 alpha and 2,3-dinor-thromboxane B-2, respectively. All biochemical parameters were measured by GC-MS and GC-MS/MS methods. T2DM patients had elevated levels of nitrate, nitrite, U-NoxR, and 8-iso-PGF(2 alpha) compared to healthy non-diabetic and normolipidemic subjects. Thirty-week treatment with atorvastatin (10 or 80 mg/d) did not significantly alter NO, PGI(2), TxA(2) and 8-iso-PGF(2 alpha) 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. (C) 2015 Elsevier Ltd. All rights reserved
AB - The present study describes the effects of atorvastatin on whole body synthesis of nitric oxide (NO), prostacyclin (PGI(2)), and thromboxane A(2) (TxA(2)), 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 (U-NoxR) served as a measure of renal CA activity. Free radical- and cyclooxygenase (COX)-catalyzed lipid peroxidation was estimated by measuring urinary 8-iso-prostaglandin F-2 alpha (8-iso-PGF(2 alpha)). In subgroups, systemic PGI(2) and TxA(2) synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-6-keto-prostaglandin F-1 alpha and 2,3-dinor-thromboxane B-2, respectively. All biochemical parameters were measured by GC-MS and GC-MS/MS methods. T2DM patients had elevated levels of nitrate, nitrite, U-NoxR, and 8-iso-PGF(2 alpha) compared to healthy non-diabetic and normolipidemic subjects. Thirty-week treatment with atorvastatin (10 or 80 mg/d) did not significantly alter NO, PGI(2), TxA(2) and 8-iso-PGF(2 alpha) 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. (C) 2015 Elsevier Ltd. All rights reserved
U2 - https://doi.org/10.1016/j.phrs.2015.01.004
DO - https://doi.org/10.1016/j.phrs.2015.01.004
M3 - Article
C2 - 25662039
SN - 1043-6618
VL - 94
SP - 1
EP - 8
JO - Pharmacological Research
JF - Pharmacological Research
ER -