Increased renal proximal convoluted tubule transport contributes to hypertension in Cyp4a14 knockout mice. Nephron Physiol 2009;113(4):p23-8
Date
08/29/2009Pubmed ID
19713718Pubmed Central ID
PMC2790762DOI
10.1159/000235774Scopus ID
2-s2.0-69149108764 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
BACKGROUND/AIMS: Disrupting the enzyme Cyp4a14 in mice leads to hypertension, which is more severe in the male mice and appears to be due to androgen excess. Because the Cyp4a14 enzyme is located in the proximal tubule of the kidney, we hypothesized that there could be dysregulation of transport in this segment that could contribute to the hypertension.
METHODS: Wild-type (SV/129) mice and mice that had targeted disruption of the Cyp4a14 gene were studied. Proximal convoluted tubules (PCT) from knockout and wild-type mice were dissected and perfused in vitrofor measurement of volume absorption (J(V)). Expression of the sodium-hydrogen exchanger 3 (NHE3), the predominant transporter responsible for sodium transport in this segment, was measured by immunoblot. Renal vascular (afferent arteriole) responses to angiotensin and endothelin were also measured.
RESULTS: PCT volume absorption was elevated in tubules from the Cyp4a14 knockout mice as compared to the wild-type mice. Brush border membrane NHE3 expression was almost 2-fold higher in Cyp4a14 knockout mice than in wild-type mice. No difference was found in the afferent arteriolar response.
CONCLUSION: Thus, hypertension in the Cyp4a14 knockout mice appears to be driven by excessive fluid reabsorption in the proximal tubule, which is secondary to overexpression of NHE3.
Author List
Quigley R, Chakravarty S, Zhao X, Imig JD, Capdevila JHMESH terms used to index this publication - Major topics in bold
AndrogensAnimals
Arterioles
Biological Transport
Blood Pressure
Cytochrome P-450 Enzyme System
Cytochrome P450 Family 4
Disease Models, Animal
Hypertension
Kidney Tubules, Proximal
Male
Mice
Mice, Knockout
Sodium
Sodium-Hydrogen Exchanger 3
Sodium-Hydrogen Exchangers
