alexa Prevention of nitrate tolerance by long-term treatment with statins.
Materials Science

Materials Science

Journal of Nanomedicine & Nanotechnology

Author(s): Fontaine D, Otto A, Fontaine J, Berkenboom G

Abstract Share this page

Abstract Recent studies have shown that statins seem to upregulate the endothelial NO synthase pathway (eNOS) and may, therefore, enhance NO availability, a direct scavenger of O2- and an inhibitor of oxidative enzymes. METHODS: To assess whether the oxidative stress produced by an in vivo exposure to nitroglycerin (NTG) is attenuated by statins, 4 groups of normocholesterolemic rats were treated; group 1 received pravastatin (20 mg/kg/d p.o) and group 2 atorvastatin (10 mg/kg/d) both for 5 weeks and the last 3 days, a cotreatment with the statin plus NTG (50 mg/kg/d, s.c. injections b.i.d.); group 3 (NTG) received only NTG (50 mg/kg/d, b.i.d. for 3 days) and group 4 served as control. Rings of thoracic aortas from these groups were studied in organ baths. Relaxations to NTG (0.1 nM to 0.1 mM) were determined on phenylephrine-preconstricted rings and O2- production (counts/10 s/mg) was assessed by lucigenin chemiluminescence technique. RESULTS: In vivo NTG exposure induced a rightward shift of the concentration-response curves to NTG: the pD2 (-log NTG concentration evoking a half maximal relaxation) was 5.8 +/- 0.3 (n=7) vs. 7.2 +/- 0.2 in the control group (not exposed to NTG, n=7) and O2- production was enhanced (1259 +/- 71 vs. 787 +/- 76, (n=5) P<.05). In contrast, groups 1 (n=7) and 2 (n=7) behaved as the control group (pD2 values were 7.4 +/- 0.1 (n=7) and 6.9 +/- 0.1 (n=7); O2- production was 721 +/- 109 and 647 +/- 121). The protective effect on nitrate tolerance disappeared when L-NAME (an eNOS inhibitor, 100 mg/kg/d) was co-administered with NTG in groups 1 and 2. Incubation of aortic rings with NAD(P)H (100 microM) also impaired the protective effect of both statins. Moreover, before NTG exposure, aortic cGMP content, reflecting EDNO availability, was significantly enhanced in group 1 (P<.05 vs. control). CONCLUSION: Long-term statin treatment protects against nitrate tolerance by counteracting NTG-induced increase in O2- production. Both eNOS pathway and NAD(P)H oxidases seem to be involved in this protective mechanism.
This article was published in Cardiovasc Drugs Ther and referenced in Journal of Nanomedicine & Nanotechnology

Recommended Conferences

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords