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. doi: 10.1152/ajprenal.00374.2004. Epub 2005 Jan 11.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • Enzyme Inhibitors
  • Creatinine
  • NG-Nitroarginine Methyl Ester