Nimodipine inhibits calcium-independent nitric oxide synthase activity in transient focal cerebral ischemia rats and cultured mouse astroglial cells
The effect of nimodipine on nitric oxide synthase (NOS) activities in brains in transient focal cerebral ischemia rats, in cultured mouse neurons and astroglial cells and bovine brain capillary endothelial cells (BCECs) was investigated. The administration of nimodipine (3 mg.kg −1, p.o., twice a da...
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Veröffentlicht in: | Life sciences (1973) 1999, Vol.65 (15), p.PL221-PL231 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | The effect of nimodipine on nitric oxide synthase (NOS) activities in brains in transient focal cerebral ischemia rats, in cultured mouse neurons and astroglial cells and bovine brain capillary endothelial cells (BCECs) was investigated. The administration of nimodipine (3 mg.kg
−1, p.o., twice a day, for 3 days) before middle cerebral artery (MCA) occlusion significantly reduced infarct size, decreased nitrite/nitrate (NO
x) content and inhibited Ca
2+-independent NOS activity in the infarct area. Nimodipine inhibited the Ca
2+-independent NOS activity induced by lipopolysaccharide (LPS) + tumor necrosis factor
α (TNF
α) in mouse astroglial cells with an IC
50 value of 0.036 ± 0.003 mM and Ca
2+-dependent NOS activity in mouse neurons with an IC
50 value of 0.047 ± 0.003 mM, but did not affect Ca
2+-dependent NOS activity in BCECs. The inhibition of Ca
2+-independent NOS activity by nimodipine in astroglial cells was competitive with respect to L-arginine. Nimodipine also inhibited the induction of Ca
2+-independent NOS activity in vitro. These results suggest that nimodipine in addition to its cerebral vasodilating effect may protect brain from ischemic neuronal damage through modifying NOS activity. |
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ISSN: | 0024-3205 1879-0631 |
DOI: | 10.1016/S0024-3205(99)00409-9 |