2000 Fiscal Year Final Research Report Summary
Molecular Pharmacological Studies on Effect of Docosahexaenoic Acid on Vascular Cell Functions
| Project/Area Number |
11672177
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Health Sciences University of Hokkaido |
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Principal Investigator |
HIRAFUJI Masahiko Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Associate Professor, 薬学部, 助教授 (20142987)
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| Co-Investigator(Kenkyū-buntansha) |
HAMAUE Naoya Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Instructor, 薬学部, 助手 (70221504)
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| Project Period (FY) |
1999 – 2000
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| Keywords | docosahexaenoic acid / eicosapentaenoic acid / vascular smooth muscle cells / nitric oxide / iNOS / prostaglandin I2 / cyclooxygenase |
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| Research Abstract |
The aim of the present project was to investigate the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), n-3 polyunsaturated fatty acids, on protein and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in cultured vascular smooth muscle cells isolated from 6-7 week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched normotensive Wistar Kyoto rats (WKY). The IL-1β-induced nitric oxide (NO) production and iNOS expression in cells of SHRSP were significantly lower than those in cells of WKY.Similarly, prostaglandins (PG)I2 production and COX-2 expression were significantly lower in cells of SHRSP than WKY, whereas there was no difference in the COX-1 expression. There were no significant differences in iNOS and COX-2 mRNA expressions between the two strains, suggesting that these protein expression may be impaired at post-transcriptional process in cells of SHRSP.DHA and EPA significantly enhanced the IL-1β-induced NO production in a concentration-dependent manner in cells of WKY, whereas had no effect in cells of SHRSP.DHA and EPA also significantly enhanced iNOS protein and mRNA expressions induced by IL-1β in cells of WKY but not in cells of SHRSP.DHA and EPA significantly increased COX-2, but not COX-1, protein expression induced by IL-1β in cells of WKY, but had no effect on COX-2 mRNA expression. These results suggest that the impairment of iNOS and COX-2 expressions in vascular smooth muscle cells may have relevance to the pathophysiology in SHRSP.These results further suggest that enhancement of NO and PGI2 productions by DHA may account for its beneficial effect on cardiovascular disorders.
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[Publications] Hirafuji, M., Minami, M., Ebihara, T., Kawahara, F., Yoshioka, M., Saito, H.and Parvez, H.S.: "Changes in intracellular Ca^<2+> signaling induced by docosahexaenoic acid in vascular smooth muscle cells from a genetical hypertensive rats (SHRSP)"Progress in Hypertension, Vol.4, Ed.by Parvez, S.H., Frossard, P.M., Minami, M., Parvez, S.and Saito, H., VSP BV, Utrecht, The Netherlands. 157-173 (1999)
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[Publications] Hirafuji, M., Kawahara, F., Ebihara, T., Nezu, A., Tanimura, A.and Minami, M.: "5-Hydroxytryptamine, but not angiotensin II, induces transient Ca^<2+> influx through Ni^<2+>-insensitive Ca^<2+> channel in rat vascular smooth muscle cells"Eur.J.Pharmacol.. 380. 163-170 (1999)
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[Publications] Hirafuji, M., Minami, M., Endo, T., Ogawa, T., Kato, K., Yoshioka, M.and Parvez, S.H.: "Intracellular regulatory mechanisms of 5-HT release from enterochromaffin cells in intestinal mucosa."Biogenic Amines. 16 (1). 29-52 (2000)
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