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Substitution of chromosome 1 ameliorates L-NAME hypertension and renal disease in the fawn-hooded hypertensive rat. Am J Physiol Renal Physiol 2005 May;288(5):F1015-22

Date

01/13/2005

Pubmed ID

15644486

DOI

10.1152/ajprenal.00374.2004

Scopus ID

2-s2.0-17644386821 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

Linkage analysis studies previously identified genetic loci associated with proteinuria and hypertension on chromosome 1 of fawn-hooded hypertensive (FHH) rats. The present studies were performed on conscious male and female rats to evaluate the influence of transfer of chromosome 1 from the Brown Norway (BN) rat to the FHH genetic background (FHH-1BN). Rats were maintained for 2 wk on 8.0% NaCl chow with NG-nitro-L-arginine methyl ester (L-NAME) in the drinking water (12.5 mg/l) to induce hypertension and accelerate the onset of renal disease. Mean arterial blood pressure (MAP) was significantly higher in the male FHH (188 +/- 3 mmHg, n = 13) compared with the BN (121 +/- 3 mmHg, n = 8); MAP in the FHH-1(BN) was midway between the two parental strains (167 +/- 5 mmHg, n = 9). Urinary protein and albumin excretion rates in the male FHH-1(BN) (Uprot = 189 +/- 36 mg/day, Ualb = 69 +/- 16 mg/day, n = 10) were also midway between levels observed in the FHH (Uprot = 485 +/- 54 mg/day; Ualb = 206 +/- 25 mg/day, n = 13) and the BN (Uprot = 32 +/- 5 mg/day, Ualb = 5 +/- 1 mg/day, n = 8). Creatinine clearance was elevated, and the degree of glomerular damage was significantly reduced in the FHH-1BN compared with the FHH. Qualitatively similar results were obtained from female FHH, FHH-1BN, and BN rats. The present results indicate that genes contributing to l-NAME-induced hypertension and renal disease are found on chromosome 1 of the FHH rat.

Author List

Mattson DL, Kunert MP, Roman RJ, Jacob HJ, Cowley AW Jr

Author

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Blood Pressure
Chromosome Mapping
Chromosomes, Mammalian
Creatinine
Disease Models, Animal
Enzyme Inhibitors
Female
Heart Rate
Hypertension, Renal
Kidney Glomerulus
Male
NG-Nitroarginine Methyl Ester
Rats
Rats, Inbred BN
Rats, Mutant Strains