Brain Edema XI pp 335-338 | Cite as
Effects of Inducible Nitric Oxide Synthase Inhibition on Cerebral Edema in Severe Hypertension
Abstract
In order to clarify the causative role of cytotoxic nitric oxide (NO) in hypertensive cerebral injury, the effects of inducible nitric oxide synthase (iNOS) inhibition on leukocytes and endothelial function were examined using stroke-prone spontaneously hypertensive rats (SHRSP).
For the iNOS inhibition, S-methylisothiourea (SMT) was administered to 12-week-old male SHRSP for 3 weeks. Immuno- histochemical examination were carried out for the expression of intercellular adehesion molecule-1 (ICAM-1), glucose transporter-1 (GLUT-1), fibrinogen and grial fibrillary acidic protein (GFAP) in cerebral cortex. The effects of iNOS inhibition was also examined for Mac-1 expression by flow cytometric analysis.
Plasma NO metabolites level was significantly lower in the SMT group than in the control group. Mac-1 expression was inhibited by SMT. In the SMT group, brain weight was significantly lower than in the control. By SMT administration, ICAM-1 expression was suppressed, GLUT-1 was enhanced, fibrinogen was decreased and GFAP was decreased as compared to those in control group.
In hypertensive cerebral injury in SHRSP, iNOS-derived NO, mainly in activated leukocytes, could be an important causative factor for endothelial injury.
Keywords
Cerebral edema hypertension nitric oxide leukocytePreview
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References
- 1.Biffl WL, Moore EE, Moore FA, Barnett CC (1996) Nitric oxide reduces endothelial expression on intercellular adhesion molecule (ICAM)-1. J Surg Res 63: 328–332PubMedCrossRefGoogle Scholar
- 2.Bredt D, Snyder SA (1994) Nitric oxide: a physiologic messenger molecule. Annu Rev Biochem 63: 175–195PubMedCrossRefGoogle Scholar
- 3.Dusting GJ (1995) Nitric oxide in cardiovascular disorders. J Vase Res 32: 143–161CrossRefGoogle Scholar
- 4.Green LC, Wanger DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Analy Biochem 126: 131–138CrossRefGoogle Scholar
- 5.Iadecola C, Zheng F, Xu S, Casey R, Ross E (1995) Inducible nitric oxide synthase gene expression in brain following cerebral ischemia. J Cereb Blood Flow Metab 15: 378–384PubMedCrossRefGoogle Scholar
- 6.Ideacola C, Zhang F, Casey R, Clark HB, Ross ME (1996) Inducible nitric oxide synthase gene expression in vasular cells after transient focal cerebral ischemia. Stroke 27: 1373–1380CrossRefGoogle Scholar
- 7.Ito H, Torii M, Suzuki T (1993) A comparative study on lipid peroxidation in cerebral cortex of stroke-prone spontaneously hypertensive and normotensive rats. Int J Biochem 25: 1801–1805PubMedGoogle Scholar
- 8.Kochanek PM, Hallenbeck JM (1992) Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke 23: 1367–1379PubMedCrossRefGoogle Scholar
- 9.Maenishi O, Ito H, Suzuki T (1997) Acceleration of hypertensive cerebral injury by the inhibition of xanthine-xanthine oxidase system in stroke-prone spontaneously hypertensive rats. Clin Exp Hypertension 19: 461–477CrossRefGoogle Scholar
- 10.Monchada S (1992) The L-arginine: nitric oxide pathway. Acta Physiol Scand 145: 201–227CrossRefGoogle Scholar
- 11.Schmid-Schonbein GW, Seiffge D, DeLano FA, Shen K, Zweifach BW (1991) Leukocyte counts and activation in spontaneously hypertensive and normotensive rats. Hypertension 17: 323–330PubMedCrossRefGoogle Scholar