The Anti-Platelet Agent, Ticlopidine, Upregulates Interleukin-1-Beta-Stimulated Nitric Oxide Production in Cultured Rat Vascular Smooth Muscle Cells
| Autor: | Eiji Kusano, J. Nemoto, Osamu Iimura, Yasushi Asano, Tetsu Akimoto, Morimasa Amemiya, Chiharu Ito, Shigeaki Muto, Makoto Inoue |
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| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Ticlopidine Vascular smooth muscle Phosphodiesterase Inhibitors Physiology Nitric Oxide Synthase Type II Nitric Oxide Muscle Smooth Vascular Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Internal medicine Cyclic AMP Genetics Animals Medicine RNA Messenger Nitrite Phosphodiesterase inhibitor Protein kinase A Cyclic GMP Aorta Cells Cultured Nitrites Nitrates business.industry Interleukin General Medicine Rats Up-Regulation Endocrinology chemistry Nephrology Nitric Oxide Synthase business cGMP-dependent protein kinase Platelet Aggregation Inhibitors Interleukin-1 medicine.drug |
| Zdroj: | Nephron Experimental Nephrology. 10:267-274 |
| ISSN: | 1660-2129 |
| Popis: | Background: Hemodialysis patients who had been treated with anti-platelet aggregation drugs, including ticlopidine, sometimes developed hypotension. The mechanism by which ticlopidine lowers the blood pressure in hemodialysis patients is unclear. To elucidate the mechanism of the action of this drug, we investigated cytokine-stimulated nitric oxide (NO) metabolism by ticlopidine in cultured rat vascular smooth muscle cells (VSMC). Methods: Nitrite, a stable metabolite of NO, and intracellular cAMP and cGMP contents were assayed by the Griess method and enzyme immunoassay, respectively. iNOS mRNA and protein expressions were analyzed by Northern blotting and Western blotting. Results: Ticlopidine enhanced interleukin-1β (IL-1β)-induced nitrite production in a dose- and time-dependent manner. The mRNA and protein expressions of inducible NO synthase were upregulated by ticlopidine in a dose- and time-dependent manner. IL-1β alone stimulated both intracellular cAMP and cGMP contents, and the addition of ticlopidine further enhanced their contents. KT 5720, a selective inhibitor of protein kinase A, but not KT 5823, a selective inhibitor of protein kinase G, abolished the enhancement of IL-1β-induced nitrite production by ticlopidine. In addition, a phosphodiesterase inhibitor, isobutylmethylxanthine, enhanced IL-1β and ticlopidine induced nitrite production. Conclusion: We concluded that ticlopidine enhanced the IL-1β-induced NO production via cAMP and subsequent activation of protein kinase A in cultured rat VSMC. |
| Databáze: | OpenAIRE |
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