Cardiovascular Protective Effects of Azelnidipine-Involvement of Nitric Oxide-
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Accession number;04A0685278
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| Title;Cardiovascular Protective Effects of Azelnidipine-Involvement of Nitric Oxide- |
| Author;
NAKAJIMA TOSHIAKI
(Univ. of Tokyo, Fac. of Med.)
TAKANO HARUHITO
(Univ. of Tokyo, Fac. of Med.)
IIDA HARUKO
(Univ. of Tokyo, Fac. of Med.)
ETO FUMIHIKO
(Univ. of Tokyo, Fac. of Med.)
IWASAWA KUNIAKI
(Univ. of Tokyo, Fac. of Med.)
KISHIDA SHIN'YA
(Univ. of Tokyo, Fac. of Med.)
JI M
(Univ. of Tokyo, Fac. of Med.)
OKUDA YUKICHI
(Univ. of Tsukuba)
MORITA TOSHIHIRO
(Univ. of Tokyo, Fac. of Med.)
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Journal Title;Japanese Pharmacology & Therapeutics
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Journal Code:Z0947A
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ISSN:0386-3603
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VOL.32;NO.8;PAGE.487-498(2004)
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| Figure&Table&Reference;FIG.9, REF.47 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Azelnidipine, a newly-developed Class III dihydropyridine Ca2+ channel blocker, has cardiovascular protective effects such as antioxidant and antiatherosclerotic effects. The effects of azelnidipine on NO production were investigated in cultured rat aortic smooth muscle cells (rat ASMCs) isolated from Wistar rats and human umbilical vein endothelial cells (HUVECs). The amounts of NO released and stable metabolite nitrite were measured by oxyhemoglobin and the Griess reaction, respectively. The release of LDH from cells was measured to evaluate cell damage. Immunocytochemical analysis was used to evaluate the expression of iNOS and nitrotyrosine protein. Azelnidipine treatment inhibited lipopolysaccaride (LPS) plus interferon-ganma (INF)-induced NO production in a concentration-dependent manner in ASMCs. Azelnidipine had the most potent inhibitory effects among the various Ca2+-blocking drugs tested (nifedipine, nicardipine, amlodipine, verapamil and diltiazem). Azelnidipine caused less inhibition of NO production already induced by LPS plus INF. Long-term treatment with LPS plus INF induced the expression of iNOS and nitrotyrosine with increased LDH release from cells. Azelnidipine and N-nitro-L-arginine methyl ester hydrochloride, a NOS inhibitor, suppressed such expression. On the other hand, azelnidipine potentiated NO production induced by eNOS in HUVECs. These results suggest that azelnidipine is a potent inhibitor of the induction of iNOS and reduces NO production in vascular smooth muscle cells. The cardiovascular protective effect of azelnidipine is probably mediated by suppression of peroxynitrite production and subsequent cell damage caused by excessive NO production. (author abst.) |
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