Effects of inducible nitric oxide synthase inhibition on cerebral edema in severe hypertension.
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. Immunohistochemical examination were carried out for the expression of intercellular adhesion molecule-1 (ICAM-1), glucose transporter-1 (GLUT-1), fibrinogen and glial 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.
Takemori
K
K
Department of Pathology, Kinki University School of Medicine, Osaka, Japan.
Ito
H
H
Suzuki
T
T
D000818:Animals; D001929:Brain Edema / Q000473:pathology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D005340:Fibrinogen / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006973:Hypertension / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000473:pathology*
D005904:Glial Fibrillary Acidic Protein; D009004:Monosaccharide Transport Proteins; D018799:Intercellular Adhesion Molecule-1; D007550:Isothiuronium; D005340:Fibrinogen; D019001:Nitric Oxide Synthase; C027744:S-methylisothiopseudouronium