Rosuvastatin treatment protects against nitrate-induced oxidative stress in eNOS knockout mice: implication of the NAD(P)H oxidase pathway.

British Journal of Pharmacology
Anne OttoGuy Berkenboom

Abstract

Nitrate tolerance is associated with an enhanced superoxide anion (O(2)(-)) production and may be attenuated by statins as they interact with the two main endothelial NO synthase (eNOS) and NAD(P)H oxidase pathways involved in this oxidative stress. Groups of wild-type (wt, C57Bl/6J) and eNOS knock-out mice (eNOS(-/-)) received rosuvastatin (20 mg kg(-1) day(-1) p.o.) for 5 weeks and a cotreatment with the statin plus nitroglycerin (NTG; 30 mg kg(-1) day(-1), subcutaneous injections b.i.d.) for the last 4 days. Another group received only NTG (30 mg kg(-1) d(-1), b.i.d. for 4 days) and finally control mice from both strains received no treatment. Rings of thoracic aortas from these groups were studied in organ baths. Relaxations to NTG (0.1 nM-0.1 mM) were determined on thromboxane analogue (U44619)-precontracted rings and O(2)(-) production (RLU 5 s(-1) mg(-1) of total protein content) was assessed in aorta homogenates with the lucigenin-enhanced chemiluminescence technique. Reverse transcriptase-polymerase chain reaction analysis was performed on aortas from both mice strains. In vivo NTG treatment induced a significant rightward shift of the concentration-effect curve to NTG compared to control group. There was, however, no ...Continue Reading

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Citations

May 8, 2013·European Journal of Pharmacology·Rajkiran Mahalwar, Deepa Khanna
Dec 19, 2015·Critical Reviews in Clinical Laboratory Sciences·Menuka Pallebage-GamarallageJohn Mamo
Dec 28, 2010·Journal of the American College of Cardiology·Andrew LiuniJohn D Parker
Apr 22, 2010·Experimental Neurology·Qing WangMidori A Yenari
Oct 29, 2008·Clinical and Experimental Pharmacology & Physiology·Stavros Selemidis
May 8, 2008·Journal of Cardiovascular Pharmacology and Therapeutics·Michael S KostapanosMoses S Elisaf
Jan 27, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Thomas ThumJohann Bauersachs
Jul 20, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·David D Gutterman
Jul 12, 2008·European Journal of Pharmacology·Magdalena DudekLidia Włodek
Feb 9, 2010·Experimental Gerontology·Rafael Luiz RechNadja Schröder
Sep 25, 2012·Heart Failure Clinics·Jeong-a KimMichael J Quon

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