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Effects of NOS inhibition on the cardiopulmonary system and brain microvascular markers after intermittent hypoxia in rats

Lookup NU author(s): Dr John Fairlie, Janet Slade, Dr Saeed Ahmed, Arthur Oakley, Professor David Barer, Professor Raj Kalaria


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We previously demonstrated that rats subjected to intermittent hypoxia (IH) by exposure to 10% O-2 for 4 h daily for 56 days in a normobaric chamber, developed pulmonary hypertension, right ventricular hypertrophy and wall-thickening in pulmonary arterioles, compared with normoxic (N) controls. These changes were greater in rats subjected to continuous hypoxia (CH breathing 10% O-2 for 56 days). Cerebral angiogenesis was demonstrated by immunostaining with glucose transporter 1 (GLUT1) antibody, in viable vessels, in CH and to a lesser degree in IH. In this study, adult Wistar rats were subjected to the same hypoxic regimes and given the nitric oxide synthase (NOS) inhibitor N-6-nitro-Larginine methyl ester (L-NAME) in drinking water (NLN, IHLN and CHLN regimes) to induce hypertension. There was significant systemic hypertension in NLN and IHLN rats, compared with N and IH, but surprisingly not in CHLN compared with CH. Hematocrit rose in all hypoxic groups (up to 79% in CHLN). There was no significant pulmonary hypertension in IHLN versus NLN rats, although there was asymmetric wall thickening in pulmonary arterioles. Cerebral GLUT1 immunoreactivity increased with L-NAME, with or without hypoxia, especially in CHLN rats, but conspicuously there was no evidence of angiogenesis in brains of IHLN compared with NLN rats. NOS blockade may attenuate the cerebral and pulmonary vascular changes of IH while augmenting cerebral angiogenesis in continuous hypoxia. However, whether cerebral effects are due to systemic hypertension or changes in cerebral nitric oxide production needs to be evaluated. (c) 2006 Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Barer GR, Fairlie J, Slade JY, Ahmed S, Laude EA, Emery CJ, Thwaites-Bee D, Oakley AE, Barer DH, Kalaria RN

Publication type: Article

Publication status: Published

Journal: Brain Research

Year: 2006

Volume: 1098

Issue: 1

Pages: 196-203

ISSN (print): 0006-8993

ISSN (electronic): 1872-6240

Publisher: Elsevier


DOI: 10.1016/j.brainres.2006.04.098


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Funder referenceFunder name
G0500247Medical Research Council