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

Authors: Roman, RJ  Hoagland, KM  Lopez, B  Kwitek, AE  Garrett, MR  Rapp, JP  Lazar, J  Jacob, HJ  Sarkis, A 
Citation: Roman RJ, etal., Am J Physiol Renal Physiol. 2006 Jan 5;.
Pubmed: (View Article at PubMed) PMID:16396943
DOI: Full-text: DOI:10.1152/ajprenal.00360.2005

The present study examined whether transfer of overlapping regions of chromosome 5 that include (4A(+)) or exclude the cytochrome P450 (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 weeks. 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, b.i.d.) 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 5-fold 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.

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RGD Object Information
RGD ID: 1578407
Created: 2006-03-17
Species: All species
Last Modified: 2006-03-17
Status: ACTIVE



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