HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/6/F1463    most recent 00360.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Roman, R. J. Articles by Sarkis, A. Search for Related Content PubMed PubMed Citation Articles by Roman, R. J. Articles by Sarkis, A.

Characterization of blood pressure and renal function in chromosome 5 congenic strains of Dahl S rats

¹Department of Physiology, ²Kidney Disease Center and ³Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin; and ⁴Department of Physiology, Medical University of Ohio, Toledo, Ohio

Submitted 1 September 2005 ; accepted in final form 2 January 2006

The present study examined whether transfer of overlapping regions of chromosome 5 that include (4A⁺) or exclude the cytochrome P-450 (CYP) 4A genes from the Lewis rat alters the renal production of 20-hydroxyeicosatetraenoic acid (20-HETE) and/or the development of hypertension in congenic strains of Dahl salt-sensitive (S) rats. The expression of CYP4A protein and the production of 20-HETE in the renal outer medulla was greater in the 4A⁺ congenic strain than the levels seen in S rats or in overlapping control congenic strains that exclude the CYP4A region. Mean arterial pressure (MAP) rose from 122 ± 2 to 190 ± 7 mmHg in S rats and from 119 ± 2 and 123 ± 2 to 189 ± 7 and 187 ± 3 mmHg in the two control congenic strains fed an 8.0% NaCl diet for 3 wk. In contrast, MAP only increased from 112 ± 2 to 150 ± 5 mmHg in the 4A⁺ congenic strain. Chronic blockade of the formation of 20-HETE with N-(3-chloro-4-morpholin-4-yl) phenyl-N'-hydroxyimido formamide (TS-011; 1 mg/kg bid) restored the salt-sensitive phenotype in the 4A⁺ congenic strain and MAP rose to 181 ± 6 mmHg after an 8.0% NaCl dietary challenge. TS-011 had no effect on the development of hypertension in S rats or the two control congenic strains. The pressure-natriuretic and diuretic responses were fivefold greater in the 4A⁺ congenic strain than in S rats. These results indicate that transfer of the region of chromosome 5 between markers D5Rat108 to D5Rat31 from the Lewis rat into the Dahl S genetic background increases the renal production of 20-HETE, improves pressure-natriuresis and opposes the development of salt-induced hypertension.

cytochrome P-450; kidney; 20-HETE

This article has been cited by other articles:

				J. M. Williams, A. Sarkis, K. M. Hoagland, K. Fredrich, R. P. Ryan, C. Moreno, B. Lopez, J. Lazar, F. J. Fenoy, M. Sharma, et al. Transfer of the CYP4A region of chromosome 5 from Lewis to Dahl S rats attenuates renal injury Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1764 - F1777. [Abstract] [Full Text] [PDF]

				N. H. Lee, B. J. Haas, N. E. Letwin, B. C. Frank, T. V. Luu, Q. Sun, C. D. House, S. Yerga-Woolwine, P. Farms, E. Manickavasagam, et al. Cross-Talk of Expression Quantitative Trait Loci Within 2 Interacting Blood Pressure Quantitative Trait Loci Hypertension, December 1, 2007; 50(6): 1126 - 1133. [Abstract] [Full Text] [PDF]

				D. E. Stec, R. J. Roman, A. Flasch, and M. J. Rieder Functional polymorphism in human CYP4F2 decreases 20-HETE production Physiol Genomics, June 19, 2007; 30(1): 74 - 81. [Abstract] [Full Text] [PDF]

				M. Yu, B. Lopez, E. A. Dos Santos, J. R. Falck, and R. J. Roman Effects of 20-HETE on Na+ transport and Na+-K+-ATPase activity in the thick ascending loop of Henle Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2400 - R2405. [Abstract] [Full Text] [PDF]