Nephrol Dial Transplant (2000) 15: 1337-1343
© 2000 European Renal Association-European Dialysis and Transplant Association
Blood pressure and the susceptibility to renal damage after unilateral nephrectomy and L-NAME-induced hypertension in rats
1 Department of Pediatric Surgery, Erasmus University Medical School, Rotterdam, The Netherlands and 2 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
Background. Fawn-hooded hypertensive (FHH) rats carry several genes which determine the susceptibility to develop renal damage, while renal damage resistant AugustxCopenhagen Irish (ACI) rats do not. Kidneys from heterozygous (FHHxACI) F1 rats, appear to be largely, but not completely, protected after blood pressure elevation with N
-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 F1 and ACI rats. Additionally, we investigated whether a general toxic effect of L-NAME, independent from a blood pressure elevation, caused renal damage in F1 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 F1 compared with ACI rats. In F1 rats, the increase in UaV per percentage incidence increase in FGS was three times higher. In LIS treated F1 rats, no significant UaV or FGS was measured at low blood pressure levels, indicating that renal damage in hypertensive F1 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.
Keywords: fawn-hooded rats; genetic susceptibility; glomerulosclerosis; hypertension; renal damage
Correspondence and offprint requests to: Richard P. E. van Dokkum PhD, Erasmus University Medical School, Department of Pediatric Surgery, Laboratory for Surgery, Room Ce 040, Dr Molewaterplein 50, Post Office Box 1738, 3000 DR Rotterdam, The Netherlands.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. L. Mattson, M. P. Kunert, R. J. Roman, H. J. Jacob, and A. W. Cowley Jr. Substitution of chromosome 1 ameliorates L-NAME hypertension and renal disease in the fawn-hooded hypertensive rat Am J Physiol Renal Physiol, May 1, 2005; 288(5): F1015 - F1022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Provoost, M. Shiozawa, R. P. E. Van Dokkum, and H. J. Jacob Transfer of the Rf-1 region from FHH onto the ACI background increases susceptibility to renal impairment Physiol Genomics, February 28, 2002; 8(2): 123 - 129. [Abstract] [Full Text] [PDF]
|
|