Chromosomal mapping of the genetic basis of hypertension and renal disease in FHH rats.
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.
Mattson
David L
DL
Dept. of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. dmattson@mcw.edu
Dwinell
Melinda R
MR
Greene
Andrew S
AS
Kwitek
Anne E
AE
Roman
Richard J
RJ
Cowley
Allen W
AW
Jacob
Howard J
HJ
D000419:Albuminuria / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D002874:Chromosome Mapping; D003404:Creatinine / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000235:genetics / Q000502:physiology; D006973:Hypertension / Q000235:genetics*; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010641:Phenotype; D011507:Proteinuria / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D012083:Renin / Q000097:blood; D012727:Sex Characteristics; D013045:Species Specificity; D014960:X Chromosome / Q000235:genetics; D014998:Y Chromosome / Q000235:genetics
D004791:Enzyme Inhibitors; D003404:Creatinine; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester