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 micrograms/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 micrograms/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 microliter/min (P less than 0.005) and renal blood flow from 2.23 +/- 0.36 to 4.25 +/- 0.65 ml/min (P less than 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 less than 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.