VERAPAMIL PROTECTION AGAINST MERCURIC CHLORIDE-INDUCED RENAL GLOMERULAR INJURY IN RATS

We have examined the effects of the calcium channel blocker verapamil on the renal glomerular structural damage produced by mercuric chlorid e in rats. Verapamil (75 mu g/kg body wt iv) was administered 30 min p rior to mercuric chloride injection (HgCl2, 5 mg/kg body wt sc). Verap amil prevented the glomerular proteinuria observed in HgCl2-treated ra ts. Isolated glomeruli from mercury-treated rats 1 h after injection p resented a diminished cross-sectional area as compared with control gl omeruli (control [mu m(2)], 26,310 +/- 2545; HgCl2 [mu m(2)], 18,474 /- 1828) and increased glomerular calcium content (control, 23 +/- 6 n mol/mg protein; HgCl2, 43 +/- 7 nmol/mg protein). Verapamil pretreatme nt prevented glomerular cross-sectional area (GCSA) diminution and glo merular calcium content rise (GCSA [mu m(2)] Vp + Hg, 28,281 +/- 4654, Ca2+ [nmol/mg protein] Vp + Hg, 18 +/- 5). Renal sections prepared fo r immunohistochemical detection and histochemical analysis showed incr eased deposits of fibronectin and lipids and enhanced cellularity in g lomerular structures from HgCl2-treated rats. Renal sections from anim als pretreated with verapamil showed fibronectin and lipid contents no t different from control sections and their histological studies did n ot show any changes when compared with control. Verapamil pretreatment also protected glomeruli from enhanced leukocyte content (myeloperoxi dase activity/mg protein): control, 59 +/- 7; HgCl2, 134 +/- 10; Vp Hg, 79 +/- 11). HgCl2 also contracts GCSA in vitro; Vp prevented this GCSA diminution. The results described in this study indicate that mer curic chloride nephrotoxicity may be associated not only with changes in renal glomerular haemodynamics, but also with a direct effect on gl omerular cells. (C) 1998 Academic Press.