VERAPAMIL LIMITS SHOCKWAVE-INDUCED RENAL TUBULAR DAMAGE IN-VIVO

Previous investigations on Madin Darby Canine Kidney (MDCK) cells demo nstrated the protective effect of verapamil against shockwave-induced tubular dysfunction. In the present study, we investigated whether ver apamil is also protective against shockwave-induced damage in vivo. Ma le rates were randomly assigned to three groups: verapamil (N = 18) (G roup 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 rec eived only anesthesics. Verapamil was given to the animals in Group I for 5 days starting 1 day before shockwave exposure. Urine was collect ed for 8 hours the day before and immediately, 1.7, and 28 days after shockwave exposure (SWE) for measurement of volume, osmolality, hemogl obin, protein, N-acetyl-beta-glucosaminidase (NAG), beta2-microglobuli n (beta2M), sodium, and creatinine. Kidneys were perfused and removed for histologic study 1,7, and 28 days after SWE in six animals of Grou ps I and II. Blood was taken in these rats (Day 1 after SWE) for the d etermination of creatinine and sodium and the calculation of the creat inine clearance (CCr) and the fractional excretion of sodium (FENa). A fter SWE, there was strong diuresis and significantly increased excret ion of NAG and beta2M in the controls, while urine osmolality decrease d. These changes were significantly less pronounced in the verapamil-t reated rats. The CCr was higher and FENa lower than in the latter grou p. 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 sh am-treated group. The biochemical and histologic results demonstrate t hat verapamil was able to ameliorate the damaging effects of high-ener gy shockwaves on renal tissue not only in vitro, but also in vivo.