Faculty Collaboration Database

Blood pressure and the susceptibility to renal damage after unilateral nephrectomy and L-NAME-induced hypertension in rats. Nephrol Dial Transplant 2000 Sep;15(9):1337-43

Date

09/09/2000

Pubmed ID

10978388

DOI

10.1093/ndt/15.9.1337

Scopus ID

2-s2.0-0033832715 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

BACKGROUND: Fawn-hooded hypertensive (FHH) rats carry several genes which determine the susceptibility to develop renal damage, while renal damage resistant August x Copenhagen Irish (ACI) rats do not. Kidneys from heterozygous (FHH x ACI) F(1) rats, appear to be largely, but not completely, protected after blood pressure elevation with N(omega)-nitro-L-arginine methyl ester (L-NAME). We examined the role of an increased haemodynamic burden on the development of renal damage combining unilateral nephrectomy (UNx)- and L-NAME-induced hypertension in F(1) and ACI rats. Additionally, we investigated whether a general toxic effect of L-NAME, independent from a blood pressure elevation, caused renal damage in F(1) rats in animals simultaneously treated with L-NAME and the ACE inhibitor lisinopril.

METHODS: Surgery was performed and L-NAME treatment (50 or 150 mg/l) was started at the age of 15 weeks. Systolic blood pressure (SBP) and urinary albumin excretion (UaV) were measured at 6 and 12 weeks post-UNx, followed by autopsy to determine the incidence of focal glomerulosclerosis (FGS). Using lisinopril (LIS) and L-NAME, another group of rats was evaluated at 12, 18, and 24 weeks after start of treatment.

RESULTS: At similar L-NAME intake, F, rats developed more severe hypertension and more UaV than ACI rats. The increase in UaV per mmHg increase in SBP was fivefold higher in F(1) compared with ACI rats. In F(1) rats, the increase in UaV per percentage incidence increase in FGS was three times higher. In LIS treated F(1) rats, no significant UaV or FGS was measured at low blood pressure levels, indicating that renal damage in hypertensive F(1) rats is not a direct effect of L-NAME, but the result of the high blood pressure or another action of the renin-angiotensin system.

CONCLUSION: We conclude that heterozygosity for the genes influencing the development of renal damage in the FHH strain increases the susceptibility of the kidney to develop damage after UNx combined with systemic hypertension.

Author List

van Dokkum RP, Jacob HJ, Provoost AP

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

Albuminuria
Animals
Blood Pressure
Enzyme Inhibitors
Genetic Predisposition to Disease
Glomerular Filtration Rate
Glomerulosclerosis, Focal Segmental
Hypertension
In Vitro Techniques
Kidney
NG-Nitroarginine Methyl Ester
Nephrectomy
Postoperative Period
Rats
Rats, Inbred Strains
Regression Analysis
Systole