Journal article
COX-2-dependent delayed dilatation of cerebral arterioles in response to bradykinin
American journal of physiology. Heart and circulatory physiology, Vol.280(5), pp.H2023-H2029
05/01/2001
DOI: 10.1152/ajpheart.2001.280.5.H2023
PMID: 11299202
Abstract
Bradykinin (BK) is released in the brain during injury and inflammation. Activation of endothelial BK receptors produces acute dilatation of cerebral arterioles that is mediated by reactive oxygen species (ROS). ROS can also modulate gene expression, including expression of the inducible isoform of cyclooxygenase (COX-2). We hypothesized that exposure of the brain to BK would produce acute dilatation, which would be followed by a delayed dilatation mediated by COX-2. To test this hypothesis in anesthetized rats, BK was placed twice in cranial windows for 7 min, after which the windows were flushed to remove residual BK. The two BK exposures were separated by 30 min. Each BK exposure produced acute dilatation of cerebral arterioles, after which diameter rapidly returned to baseline. Over the subsequent 4.5 h after the second BK exposure, arterioles dilated 48 ± 8%. Treatment of the cranial window with NS-398, a selective COX-2 inhibitor, or dexamethasone, significantly attenuated the delayed dilatation. Aminoguanidine, a selective inhibitor of inducible nitric oxide synthase, did not alter the delayed dilatation. Cotreatment of cranial windows with BK, superoxide dismutase, and catalase also prevented the delayed dilatation. In separate experiments, exposure of the cortical surface to BK upregulated leptomeningeal expression of COX-2 mRNA. Our results suggest that acute, time-limited exposure of the brain to BK produces delayed dilatation of cerebral arterioles dependent on expression and activity of COX-2.
Details
- Title: Subtitle
- COX-2-dependent delayed dilatation of cerebral arterioles in response to bradykinin
- Creators
- Johnny E Brian - Departments of AnesthesiaFrank M Faraci - Internal Medicine and Pharmacology, andSteven A Moore
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.280(5), pp.H2023-H2029
- DOI
- 10.1152/ajpheart.2001.280.5.H2023
- PMID
- 11299202
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Language
- English
- Date published
- 05/01/2001
- Academic Unit
- Pathology; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040478002771
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