Characterization of blood pressure and renal function in chromosome 5 congenic strains of Dahl S rats. Am J Physiol Renal Physiol 2006 Jun;290(6):F1463-71
Date
01/07/2006Pubmed ID
16396943DOI
10.1152/ajprenal.00360.2005Scopus ID
2-s2.0-33744790877 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
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.
Author List
Roman RJ, Hoagland KM, Lopez B, Kwitek AE, Garrett MR, Rapp JP, Lazar J, Jacob HJ, Sarkis AAuthor
Anne E. Kwitek PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlood Pressure
Cytochrome P-450 CYP4A
Hemodynamics
Hydroxyeicosatetraenoic Acids
Hypertension
Kidney
Kidney Medulla
Male
Rats
Rats, Inbred Dahl
Rats, Inbred Lew
Sodium Chloride, Dietary
Time Factors