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

Abstract

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.

• Authors: Richard J Roman, Kimberly M Hoagland, Bernardo Lopez, Anne E Kwitek, Michael R Garrett, John P Rapp, Josef Lazar, Howard J Jacob, Albert Sarkis
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 290 Issue 6 Pg. F1463-71 (Jun 2006) ISSN: 1931-857X [Print] United States
• PMID: 16396943 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxyeicosatetraenoic Acids
• Sodium Chloride, Dietary
• 20-hydroxy-5,8,11,14-eicosatetraenoic acid
• Cytochrome P-450 CYP4A

Topics

• Animals
• Blood Pressure (genetics)
• Cytochrome P-450 CYP4A (genetics, metabolism)
• Hemodynamics
• Hydroxyeicosatetraenoic Acids (biosynthesis)
• Hypertension (genetics)
• Kidney (blood supply, enzymology)
• Kidney Medulla (enzymology)
• Male
• Rats
• Rats, Inbred Dahl
• Rats, Inbred Lew
• Sodium Chloride, Dietary (administration & dosage)
• Time Factors