Platelet Nitric Oxide and Superoxide Release During the Development of Nitrate Tolerance
| Autor: | Adrian Devine, C G Hanratty, Lawrence T. McGrath, David G.A. Morgan, Lana J. Dixon, Martin Wilson, Gary E. McVeigh, Paul Hamilton, William J. Leahey |
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| Rok vydání: | 2002 |
| Předmět: |
Oxidase test
biology Superoxide business.industry Biological activity Pharmacology Nitric oxide Nitric oxide synthase chemistry.chemical_compound Biochemistry chemistry Drug tolerance Physiology (medical) biology.protein Medicine Platelet Cardiology and Cardiovascular Medicine business Cyclic guanosine monophosphate |
| Zdroj: | Circulation. 106:208-213 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.0000021600.84149.78 |
| Popis: | Background — The therapeutic benefits that accompany the continuous administration of organic nitrates are attenuated by the development of tolerance to the compounds. Altered superoxide production and NO bioavailability have been implicated in contributing to the development of tolerance, an effect that may be ameliorated by the administration of antioxidants. Methods and Results — We studied the effect of 3 days of continuous transdermal administration of nitroglycerin (NTG) (10 mg/24 hours) on platelet free radical (NO and superoxide anion [O 2 ·− ] activity) with and without coadministration of supplemental ascorbate (2.4 g/24 hours). NAD(P)H oxidase activity, nitric oxide synthase (NOS) activity, and cyclic guanosine monophosphate (cGMP) content were also assessed. Radial artery pressure pulse waveforms were used to track the hemodynamic actions of NTG. Three days of NTG/placebo was associated with a significant increase in platelet NO and O 2 ·− production from 1.0±1.17 to 2.52±0.88 pmol/10 8 platelets and 13.2±4.8 to 72.5±34.4 pmol/10 8 platelets, respectively ( P 2 ·− min/mg protein and cGMP content from 0.60±0.10 to 0.89±0.16 pmol/10 9 platelets ( P 2 ·− release in platelets. Conclusions — Three days of continuous transdermal administration of NTG was accompanied by increased platelet NO and O 2 ·− production and NADH oxidase activity that was suppressed by coadministration of oral ascorbate. Although a significant degree of tolerance would be expected during continuous nitrate administration, a residual hemodynamic action could be identified by arterial pulse contour analysis. |
| Databáze: | OpenAIRE |
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