Hypertension After Neonatal Uninephrectomy in Rats Precedes Glomerular Damage

Abstract

The present study was designed to determine whether adult hypertension caused by a reduced number of nephrons from birth is due to preceding glomerular damage. Newborn male Sprague-Dawley rat pups were uninephrectomized during the first 24 hours after birth (UNX rats). At 20 weeks of age, chronically instrumented UNX animals were hypertensive on a normal-sodium (0.20%) diet compared with sham-operated controls (142±2 versus 124±2 mm Hg in controls). Body weights and the total kidney-to–body weight ratio were not significantly different in adult UNX animals compared with controls. Glomerular filtration rate (GFR) was reduced by 49% in UNX rats (1.85±0.24 versus 3.65±0.22 mL/min). Urine protein excretions were higher in UNX rats (20±2 versus 7±1 mg/d in controls). On a high-sodium (3.15%) diet, arterial pressure increased more in UNX than in controls (28±9 versus 3±1 mm Hg). In contrast, in animals studied at 8 weeks of age, GFR was only reduced by 26% in UNX animals (2.02±0.06 versus 2.73±0.07 mL/min). Their hypertension (125±2 versus 117±2 mm Hg) was also salt sensitive (increase on high-sodium diet of 35±11 versus 8±2 mm Hg in controls) but was not associated with proteinuria or histological signs of glomerular disease. Number of glomeruli per kidney in UNX animals was not different from controls, but individual glomerular volume increased by 41%. Thus, surgical removal of 50% of the nephrons, when done during development, causes reduced renal function and salt-sensitive hypertension in adulthood. Hypertension is present earlier in life than signs of glomerular disease, which suggests that hypertension is a major contributor to rather than primarily resulting from onset of renal disease.