Salt-sensitive hypertension is associated with dysfunctional Cyp4a10 gene and kidney epithelial sodium channel
- Authors
- Nakagawa K.; Holla V.R.; Wei Y.; Wang W.-H.; Gatica A.; Wei S.; Mei S.; Miller C.M.; Dae R.C.; Price Jr. E.; Zent R.; Pozzi A.; Breyer M.D.; Guan Y.; Falck J.R.; Waterman M.R.; Capdevila J.H.
- Issue Date
- 2006
- Citation
- Journal of Clinical Investigation, v.116, no.6, pp 1696 - 1702
- Pages
- 7
- Indexed
- SCOPUS
- Journal Title
- Journal of Clinical Investigation
- Volume
- 116
- Number
- 6
- Start Page
- 1696
- End Page
- 1702
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/19319
- DOI
- 10.1172/JCI27546
- ISSN
- 0021-9738
1558-8238
- Abstract
- Functional and biochemical data have suggested a role for the cytochrome P450 arachidonate monooxygenases in the pathophysiology of hypertension, a leading cause of cardiovascular, cerebral, and renal morbidity and mortality. We show here that disruption of the murine cytochrome P450, family 4, subfamily a, polypeptide 10 (Cyp4a10) gene causes a type of hypertension that is, like most human hypertension, dietary salt sensitive. Cyp4a10-/- mice fed low-salt diets were normotensive but became hypertensive when fed normal or high-salt diets. Hypertensive Cyp4a10-/- mice had a dysfunctional kidney epithelial sodium channel and became normotensive when administered amiloride, a selective inhibitor of this sodium channel. These studies (a) establish a physiological role for the arachidonate monooxygenases in renal sodium reabsorption and blood pressure regulation, (b) demonstrate that a dysfunctional Cyp4a10 gene causes alterations in the gating activity of the kidney epithelial sodium channel, and (c) identify a conceptually novel approach for studies of the molecular basis of human hypertension. It is expected that these results could lead to new strategies for the early diagnosis and clinical management of this devastating disease.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 2. Clinical Science > Department of Nephrology and Hypertension > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.