Glomerular hemodynamic adaptations in remnant nephrons: effects of verapamil

Abstract

Chronic verapamil administration has been shown to reduce the renal dysfunction, glomerular sclerosis, and mortality in partially nephrectomized rats; the mechanism is unknown. Therefore, the present micropuncture study examines the effect of verapamil on glomerular hemodynamics of Munich-Wistar rats 4 wk after five-sixths nephrectomy. Whole-kidney function was similar in nephrectomized rats treated with verapamil (Nx-VER) and saline (Nx-SAL), and glomerular filtration rate (GFR) was one-third of control. Both Nx-VER and Nx-SAL rats exhibited a similar degree of glomerular hyperperfusion and hyperfiltration. However, mean glomerular capillary hydrostatic pressure difference (delta P) was lower in Nx-VER than Nx-SAL rats (42.4 +/- 1.2 vs. 47.2 +/- 1.0 mmHg, P less than 0.005) because of an increase in Bowman's space hydrostatic pressure (PBS) in Nx-VER rats (15.5 +/- 0.8 vs. Nx-SAL 11.9 +/- 0.7 mmHg, P less than 0.005). Glomerular ultrafiltration coefficient (LpA) was significantly lower in Nx-SAL (P less than 0.005) than in Nx-VER or control rats. Urinary protein excretion and the magnitude of glomerular sclerosis in Nx-SAL and Nx-VER rats were not different. In conclusion, chronic VER administration normalizes LpA and reduces delta P, by increasing PBS, in Nx rats, alterations that neutralize each other, leading to the constancy of single-nephron GFR.