Protective effect of verapamil in cyclosporin-incubated human and murine isolated glomeruli.

Abstract

Cyclosporin A (CsA)-induced nephrotoxicity is characterized by a decrease in the glomerular filtration rate (GFR) which is associated with a large increase in renal vascular resistance (RVR). Using a video image analyzer, we have demonstrated CsA-induced glomerular vasoconstriction in rat isolated glomeruli as assessed by a significant reduction of glomerular area. This vasoactive response explains in part the renal hemodynamic changes and the development of CsA-induced reversible decline in renal function. To confirm the direct vasoactive effect of CsA on glomeruli and to determine if calcium-blocking agents modified this response, we compared the changes in area of isolated rat and human glomeruli incubated either with CsA alone or with CsA plus verapamil. The area of the isolated glomeruli was quantitatively evaluated by a camera video image analyzer; each glomerulus served as its own control. Area kinetics were studied at 5 min intervals over 30 min. CsA-induced glomerular size reduction is dose dependent (-4.2% for 10(-10) M and -10.2% for 10(-6) M) and time dependent (-2.3% at 5 min, -4.7% at 10 min, and -12.1% at 30 min for 10(-6) M). With verapamil pretreatment, CsA-induced reduction in glomerular size was reduced (-0.6% and -3.6%, respectively, for 10(-6) M and 10(-7) M verapamil). Thus, verapamil can be considered as a protective agent against CsA-induced vasoconstriction in rat and human isolated glomeruli.