EFFECTS OF THE PROSTAGLANDIN E1 ANALOG MISOPROSTOL ON CYCLOSPORINE NEPHROTOXICITY

Abstract

Acute infusion of cyclosporine in rats causes intense renal vasoconstriction and decreased glomerular filtration rate, effects that persist during short-term daily administration. We tested whether the orally active prostaglandin E1 analog misoprostol could reverse cyclosporine-induced renal vasoconstriction and restore the glomerular filtration rate. Male Sprague-Dawley rats were infused with cyclosporine (10 mg/kg) and then given an oral dose of misoprostol (100, 500, or 1000 .mu.g/kg). Cyclosporine caused large decreases in glomerular filtration rate and renal blood flow and a large increase in renal vascular resistance. Misoprostol decreased renal vascular resistance and increased renal blood flow and glomerular filtration rate to near normal levels. The two highest doses of misoprostol caused severe hypotension only in cyclosporine-treated animals. However, when it was given in a dose of 100 .mu.g/kg hypotension was not a serious problem. This dose of misoprostol resulted in an increase in glomerular filtration rate from 341 .+-. 57 to 669 .+-. 104 .mu.l/min (P < 0.005) and renal blood flow from 2.23 .+-. 0.36 to 4.25 .+-. 0.65 ml/min (P < 0.01), as well as a decrease in renal vascular resistance from 73.7 .+-. 23.8 to 29.4 .+-. 5.8 mmHg/ml/min (P < 0.05) in cyclosporine-treated animals. When given to control animals, misoprostol had no effects on renal hemodynamics or renal function. In summary, acute cyclosporine-induced renal vasoconstriction and renal dysfunction in the rat were substantially reversed by oral administration of the prostaglandin E1 analog misoprostol.