DOI: 10.1038/jcbfm.1995.6. Marked Induction of Calcium-Independent Nitric Oxide Synthase Activity after Focal Cerebral Ischemia

Marked Induction of Calcium-Independent Nitric Oxide Synthase Activity after Focal Cerebral Ischemia

10.1038/jcbfm.1995.6

Crossref journal-article

SAGE Publications

Journal of Cerebral Blood Flow & Metabolism (179)

Abstract

We studied the effect of focal cerebral ischemia on inducible (iNOS) and constitutive (cNOS) nitric oxide synthase enzymatic activities in the affected brain. The middle cerebral artery (MCA) was occluded in spontaneously hypertensive rats. Animals were killed 1, 2, 4, and 7 days later. cNOS and iNOS enzymatic activities were determined in the infarcted cortex using the assay of Bredt and Snyder. cNOS was assayed in the presence of calcium, whereas iNOS was assayed in the absence of calcium and in the presence of tetrahydrobiopterin. The validity of the iNOS assay was verified in rats treated with bacterial lipopolysaccharide. In these animals, the magnitude of the induction of iNOS enzymatic activity in lung, spleen, and brain paralleled the expression of iNOS mRNA, assessed by reverse-transcription polymerase chain reaction. After MCA occlusion, calcium-dependent (cNOS) activity was markedly reduced only in lesioned cerebral cortex at days 1–7 ( p < 0.001; analysis of variance and Tukey's test). In contrast to cNOS, calcium-independent (iNOS) activity was induced substantially in the infarct ( p < 0.005) but not in the contralateral intact cortex ( p > 0.05). iNOS activity peaked at day 2 and was not different from baseline at day 7 ( p > 0.05). No NADPH diaphorase-positive neurons were observed in the area of the lesion at days 1–7. Macrophages appeared at day 2 and invaded the infarcted tissue by day 7. At this time, numerous glial fibrillary acidic protein-positive astrocytes were observed within the lesion. The results suggest that the decline in calcium-dependent (cNOS) activity reflects loss of NOS neurons within the lesion. The induction of calcium-independent activity is likely to reflect induction of iNOS in nonneuronal cells. Sustained nitric oxide production by iNOS may contribute to the late phase of tissue damage in focal cerebral ischemia.

Bibliography

Iadecola, C., Xu, X., Zhang, F., El-Fakahany, E. E., & Ross, M. E. (1995). Marked Induction of Calcium-Independent Nitric Oxide Synthase Activity after Focal Cerebral Ischemia. Journal of Cerebral Blood Flow & Metabolism, 15(1), 52â59.

Authors 5

Costantino Iadecola (first)
Xiaohong Xu (additional)
Fangyi Zhang (additional)
Esam E. El-Fakahany (additional)
M. Elizabeth Ross (additional)

References 30 Referenced 189

10.1073/pnas.87.4.1620
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10.1007/BF00227730
10.4049/jimmunol.150.7.2964 / J Immunol by Dimmeler S (1993)
{'key': 'bibr8-jcbfm.1995.6', 'first-page': '623', 'volume': '142', 'author': 'Garcia JH', 'year': '1993', 'journal-title': 'Am J Pathol'} / Am J Pathol by Garcia JH (1993)
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10.1007/BF00967330
10.1073/pnas.85.15.5698
10.1042/bj2700833
10.1073/pnas.89.14.6348
10.1006/bbrc.1993.2380
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10.1006/bbrc.1993.2398
10.1016/S0021-9258(18)31375-9
10.1096/fasebj.6.12.1381691
{'key': 'bibr24-jcbfm.1995.6', 'first-page': '287', 'volume': '65', 'author': 'Stuehr DJ', 'year': '1992', 'journal-title': 'Adv Enzymol Relat Areas Mol Biol'} / Adv Enzymol Relat Areas Mol Biol by Stuehr DJ (1992)
10.1016/S0022-3565(25)38153-X / J Pharmacol Exp Ther by Szabo C (1993)
10.1097/00001756-199305000-00024
10.1038/jcbfm.1994.71
10.1038/jcbfm.1994.28
10.1126/science.8080500
10.1161/01.STR.24.12.2016

Dates

Type	When
Created	14 years, 4 months ago (April 8, 2011, 1:19 p.m.)
Deposited	5 months, 2 weeks ago (March 10, 2025, 9:22 p.m.)
Indexed	1 month, 3 weeks ago (July 6, 2025, 1:27 p.m.)
Issued	30 years, 7 months ago (Jan. 1, 1995)
Published	30 years, 7 months ago (Jan. 1, 1995)
Published Online	30 years, 7 months ago (Jan. 1, 1995)
Published Print	30 years, 7 months ago (Jan. 1, 1995)

Funders 0

None

BibTeX

@article{Iadecola_1995, title={Marked Induction of Calcium-Independent Nitric Oxide Synthase Activity after Focal Cerebral Ischemia}, volume={15}, ISSN={1559-7016}, url={http://dx.doi.org/10.1038/jcbfm.1995.6}, DOI={10.1038/jcbfm.1995.6}, number={1}, journal={Journal of Cerebral Blood Flow & Metabolism}, publisher={SAGE Publications}, author={Iadecola, Costantino and Xu, Xiaohong and Zhang, Fangyi and El-Fakahany, Esam E. and Ross, M. Elizabeth}, year={1995}, month=jan, pages={52–59} }

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  "abstract": "<jats:p>We studied the effect of focal cerebral ischemia on inducible (iNOS) and constitutive (cNOS) nitric oxide synthase enzymatic activities in the affected brain. The middle cerebral artery (MCA) was occluded in spontaneously hypertensive rats. Animals were killed 1, 2, 4, and 7 days later. cNOS and iNOS enzymatic activities were determined in the infarcted cortex using the assay of Bredt and Snyder. cNOS was assayed in the presence of calcium, whereas iNOS was assayed in the absence of calcium and in the presence of tetrahydrobiopterin. The validity of the iNOS assay was verified in rats treated with bacterial lipopolysaccharide. In these animals, the magnitude of the induction of iNOS enzymatic activity in lung, spleen, and brain paralleled the expression of iNOS mRNA, assessed by reverse-transcription polymerase chain reaction. After MCA occlusion, calcium-dependent (cNOS) activity was markedly reduced only in lesioned cerebral cortex at days 1\u20137 ( p &lt; 0.001; analysis of variance and Tukey's test). In contrast to cNOS, calcium-independent (iNOS) activity was induced substantially in the infarct ( p &lt; 0.005) but not in the contralateral intact cortex ( p &gt; 0.05). iNOS activity peaked at day 2 and was not different from baseline at day 7 ( p &gt; 0.05). No NADPH diaphorase-positive neurons were observed in the area of the lesion at days 1\u20137. Macrophages appeared at day 2 and invaded the infarcted tissue by day 7. At this time, numerous glial fibrillary acidic protein-positive astrocytes were observed within the lesion. The results suggest that the decline in calcium-dependent (cNOS) activity reflects loss of NOS neurons within the lesion. The induction of calcium-independent activity is likely to reflect induction of iNOS in nonneuronal cells. Sustained nitric oxide production by iNOS may contribute to the late phase of tissue damage in focal cerebral ischemia.</jats:p>",
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