Faculty Collaboration Database

Chromosomal mapping of the genetic basis of hypertension and renal disease in FHH rats. Am J Physiol Renal Physiol 2007 Dec;293(6):F1905-14

Date

09/28/2007

Pubmed ID

17898042

DOI

10.1152/ajprenal.00012.2007

Scopus ID

2-s2.0-36549060031 (requires institutional sign-in at Scopus site)   41 Citations

Abstract

This study examined the genetic basis for hypertension and renal disease phenotypes in Fawn Hooded hypertensive (FHH) rats using chromosome substitution strains (consomic rats) in which each of the 20 autosomes as well as the X and Y chromosomes were transferred from the normal Brown Norway (BN) rat onto the FHH genetic background. Male and female rats of each of the parental and consomic strains were maintained for 2 wk on high-salt (8.0% NaCl) chow with N(G)-nitro-l-arginine methyl ester (l-NAME) in the drinking water (12.5 mg/l) to induce hypertension and renal disease. Mean arterial blood pressure (MAP) was significantly higher (by over 60 mmHg) in the male FHH compared with BN rats. Urinary protein and albumin excretion rates were increased by 15- and 40-fold, respectively, in the male FHH compared with the BN. Plasma renin activity was 10-fold higher in the FHH than the BN. Similar significant differences were observed between the female FHH and BN, but the degree of hypertension and proteinuria was of a lesser magnitude. Substitution of chromosome 20 from the BN to the FHH attenuated the development of l-NAME-induced hypertension, normalized plasma renin activity, and decreased plasma creatinine in male rats. In female rats, substitution of chromosome 15 decreased MAP and urinary protein excretion. Urinary excretion of albumin in males was decreased by substitution of chromosomes 1, 15, 16, and 18 from the BN into the FHH genetic background. The present data indicate that genes that can modify l-NAME-induced hypertension and proteinuria are on chromosomes 1, 15, 16, 18, and 20.

Author List

Mattson DL, Dwinell MR, Greene AS, Kwitek AE, Roman RJ, Cowley AW Jr, Jacob HJ

Authors

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Melinda R. Dwinell PhD Professor in the Physiology department at Medical College of Wisconsin
Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin

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

Albuminuria
Animals
Blood Pressure
Chromosome Mapping
Creatinine
Enzyme Inhibitors
Female
Heart Rate
Hypertension
Kidney Diseases
Male
NG-Nitroarginine Methyl Ester
Phenotype
Proteinuria
Rats
Rats, Inbred BN
Renin
Sex Characteristics
Species Specificity
X Chromosome
Y Chromosome