Verapamil Limits Shockwave-Induced Renal Tubular Damage in Vivo*

Abstract

Previous investigations on Madin Darby Canine Kidney (MDCK) cells demonstrated the protective effect of verapamil against shockwave-induced tubular dysfunction. In the present study, we investigated whether verapamil is also protective against shockwave-induced damage in vivo. Male rates were randomly assigned to three groups: verapamil (N = 18) (Group I), control (N = 18) (Group II), or sham treatment (N = 4) (Group III). Groups I and II were treated with 500 Shockwaves to each kidney with the Dornier MFL 5000 at 18 kV. Animals assigned to Group III received only anesthesics. Verapamil was given to the animals in Group I for 5 days starting 1 day before shockwave exposure. Urine was collected for 8 hours the day before and immediately, 1.7, and 28 days after shockwave exposure (SWE) for measurement of volume, osmolality, hemoglobin, protein, N-acetyl-β-glucosaminidase (NAG), β2-microglobulin (β2M), sodium, and creatinine. Kidneys were perfused and removed for histologic study 1,7, and 28 days after SWE in six animals of Groups I and II. Blood was taken in these rats (Day 1 after SWE) for the determination of creatinine and sodium and the calculation of the creatinine clearance (CCr) and the fractional excretion of sodium (FENa). After SWE, there was strong diuresis and significantly increased excretion of NAG and β2M in the controls, while urine osmolality decreased. These changes were significantly less pronounced in the verapamil-treated rats. The CCr was higher and FENa lower than in the latter group. Histologic study demonstrated dilation of the intrarenal veins and tubules and swelling, vacuolization, and potocytosis of the epithelial cells. These alterations were more pronounced in the control animals than in the verapamil-treated rats. No changes were observed in the shamtreated group. The biochemical and histologic results demonstrate that verapamil was able to ameliorate the damaging effects of high-energy shockwaves on renal tissue not only in vitro, but also in vivo.