Faculty Collaboration Database

Genetic differences define severity of renal damage after L-NAME-induced hypertension in rats. J Am Soc Nephrol 1998 Mar;9(3):363-71

Date

03/26/1998

Pubmed ID

9513898

DOI

10.1681/ASN.V93363

Scopus ID

2-s2.0-0031890319 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

Genetic factors are important in determining the susceptibility to renal damage. In a backcross of the hypertensive and proteinuric fawn-hooded Erasmus University Rotterdam (FHH/EUR) rat with the normotensive, nonproteinuric August Copenhagen Irish (ACI/EUR) rat, two genes (denoted Rf-1 and Rf-2) were genetically mapped for parameters of functional and structural renal damage. The aim of the present study was to investigate the susceptibility to functional and structural renal damage in heterozygous (FHH X ACI) F1 rats compared with the parental FHH and ACI strains at similar levels of systolic BP (SBP). BP elevation was induced by chronic treatment with NG-nitro-L-arginine methyl ester (L-NAME) in either a low dose (LD, 75 to 100 mg/L) or a high dose (HD, 175 to 250 mg/L) in the drinking fluid. Survival of FHH rats and, to a lesser extent, F1 rats, was adversely affected by L-NAME treatment. All ACI rats except for one ACI-HD animal survived. In all strains, L-NAME caused a dose-dependent increase in SBP. At similar levels of SBP, the increase in functional renal damage, as indicated by the level of albuminuria, was higher in F1 compared with ACI, but lower compared with FHH. The same differences were found for the level of structural renal damage, as indicated by the incidence of glomerulosclerosis. Both the SBP and the average BP burden (SBP-Av), defined as SBP averaged over the period of follow-up, directly correlated with the level of albuminuria and incidence of glomerulosclerosis in all strains. However, the increase in the degree of renal damage per mmHg increase in SBP or SBP-Av was significantly higher in the F1 rats compared with ACI, but lower compared with FHH rats. Values for these F1 rats were closer to the ACI rats than to values for the FHH rats and increased above an SBP level of 180 mmHg. The F1 rats, being heterozygous for Rf-1 and Rf-2, as well as for other potential genes responsible for renal disease, were largely, but not completely, protected from hypertension-induced renal damage. It is concluded that complete susceptibility to hypertension-associated renal damage in rats primarily depends on the presence of predisposing genes for renal failure even after a significant increase in BP.

Author List

Van Dokkum RP, Jacob HJ, Provoost AP

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

Animals
Autopsy
Blood Pressure
Body Weight
Creatinine
Glomerulosclerosis, Focal Segmental
Humans
Hypertension, Renal
Incidence
Infant
NG-Nitroarginine Methyl Ester
Rats
Rats, Inbred Strains
Regression Analysis
Renal Insufficiency
Severity of Illness Index
Species Specificity
Survival
Systole