title: Possible role of nitric oxide generated by leukocytes in the pathogenesis of hypertensive cerebral edema in stroke-prone spontaneously hypertensive rats.
abstract: We investigated the mechanisms responsible for cerebral edema in stroke-prone spontaneously hypertensive rats (SHRSP), including leukocyte activation and nitric oxide (NO) generation, both in vivo and in vitro. We also investigated the effects of angiotensin II (AngII) on leukocyte function in relation to NO production. Leukocyte-endothelial cell adhesion in brain microvessels was investigated by electron tomography using ultra-high voltage electron microscopy. Electron tomography clearly showed that leukocytes had well-developed intracellular organelles and abundant microvilli that were tangled with the endothelial cells in brain microvessels. Under confocal microscopic examination, diaminofluorescein-2 (a NO indicator)-positive cells were closely localized to anti-granulocyte-positive cells. The fluorescence intensity was much stronger in SHRSP than in age-matched Wistar-Kyoto (WKY) rats, as a normotensive control. Mac-1 (leukocyte integrin, CD11b/CD18), angiotensin type 1 (AT1) receptor and inducible nitric oxide synthase (iNOS) expression was higher (or tended to be higher) in SHRSP leukocytes than in WKY leukocytes. The plasma NO metabolite content was also higher in SHRSP than in WKY rats. All of these factors were upregulated by AngII stimulation. Furthermore, NO release from leukocytes was enhanced by AngII or lipopolysaccharide through NF-κB activation, but was suppressed by an AT1 receptor blocker or s-methyl-isothiourea. The present study revealed that one of the causative factors for cerebral edema in SHRSP rats is the generation of NO radicals by iNOS activated via NF-κB in AngII-stimulated leukocytes. Thus, the pathogenesis of cerebral edema in SHRSP is likely to involve inflammatory processes mediated by AngII.
authors: Department of Food and Nutrition, Kinki University Faculty of Agriculture, 3327-204 Nakamachi, Nara 631-8505, Japan. kuriman@nara.kindai.ac.jp
authors: Kumiko
authors: K
authors: Takemori
authors: Takao
authors: T
authors: Inoue
authors: Hiroyuki
authors: H
authors: Ito
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001929:Brain Edema / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D016328:NF-kappa B; D000804:Angiotensin II; D009569:Nitric Oxide