Substitution of chromosome 1 ameliorates L-NAME hypertension and renal disease in the fawn-hooded hypertensive rat.
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.
Mattson
David L
DL
Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. dmattson@mcw.edu
Kunert
Mary Pat
MP
Roman
Richard J
RJ
Jacob
Howard J
HJ
Cowley
Allen W
AW
D000818:Animals; D001794:Blood Pressure; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors; D005260:Female; D006339:Heart Rate; D006977:Hypertension, Renal / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D051381:Rats; D011914:Rats, Inbred BN; D011922:Rats, Mutant Strains
D004791:Enzyme Inhibitors; D003404:Creatinine; D019331:NG-Nitroarginine Methyl Ester