Prevention of cyclosporin-induced vasoconstrictive effect in rat isolated glomeruli with pharmacological vasoactive...

This study was designed to demonstrate the ability of some physiological or pharmacological agents to diminish or even suppress the vasoconstrictive effects of cyclosporin (CsA) in rat isolated glomeruli. The area of glomeruli isolated from the superficial cortex of male Sprague-Dawley rats was assessed by an image analyser with a video camera. Each glomerulus was imaged before treatment and 5, 10, 15, 20 and 30 min after incubation with CsA alone or in association with another vasoactive agent. CsA alone induced a marked time- and dose-dependent decrease in glomerular area (-4.7% at 10 min, -10.3% at 20 min and -12.0% at 30 min); cremophore or control solute did not induce any decrease. CsA with 10(-6)m-verapamil brought about only a slight decrease (-1.5% at 10 min, -3.0% at 20 min and -4.8% at 30 min), as was the case with 10(-8)m-prostacyclin analogue (Iloprost) (-1% at 10 min, -1.8% at 20 min and -3.4% at 30 min); finally, 10(-6)m-thromboxane synthesis inhibitor (CGS 12970) brought about a reduction in area of -2% at 10 min, -3.6% at 20 min and -4.3% at 30 min. In conclusion, the marked vasoconstriction induced by CsA in rat isolated glomeruli can be partially prevented by various pharmacological vasoactive agents that act on different vascular targets of CsA.