Genetic differences define severity of renal damage after L-NAME-induced hypertension in rats

被引:0
作者
Van Dokkum, RPE
Jacob, HJ
Provoost, AP
机构
[1] Erasmus Univ, Sch Med, Dept Pediat Surg, NL-3000 DR Rotterdam, Netherlands
[2] Med Coll Wisconsin, Dept Physiol, Lab Genet Res, Milwaukee, WI 53226 USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 1998年 / 9卷 / 03期
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D O I
暂无
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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 N-G-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 followup, 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.
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页码:363 / 371
页数:9
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