Antagonist capacities of nifedipine, captopril, phenoxybenzamine, prostacyclin and indomethacin on cyclosporin A induced impairment of rat renal function.
Experimental evidence indicates that cyclosporin A (CyA) nephrotoxicity is due to renal arteriolar constriction, reducing renal blood flow, glomerular filtration rate (GFR), and delivery of tubular fluid from the end of the proximal tubule to the loop of Henle. The proximal tubular fractional reabsorption (PFR) is increased. Therefore, the impact on renal function of vasodilating agents was studied in rats given CyA. Conscious catheterized rats and clearance techniques were used. In acute experiments a preexisting CyA-nephrotoxicity was resistant to infusion of phenoxybenzamine, prostacyclin, captopril, nifedipine and indomethacin. Concomitant treatment with captopril and CyA did not improve renal function, while concomitant treatment with CyA and nifedipine improved GFR to 1.13 +/- 0.34 ml min-1 g-1 kidney weight (gKW) (n = 19, P less than 0.05), as compared to CyA and placebo treated controls (n = 12, 0.83 +/- 0.32 ml min-1 g-1 KW). Nifedipine also reduced FPR (88.6 +/- 5.1% vs. 83.2 +/- 5.6%. P less than 0.01), and increased lithium clearance from 99 +/- 54 to 184 +/- 64 microliters min-1 g-1 KW (P less than 0.001). The results are further evidence that CyA nephrotoxicity includes renal vasoconstriction, and indicates that calcium entry blockade is nephroprotective in the case of CyA toxicity.
D000818:Animals; D002216:Captopril / Q000494:pharmacology; D003524:Cyclosporins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011464:Epoprostenol / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D003524:Cyclosporins; D014665:Vasodilator Agents; D010643:Phenoxybenzamine; D002216:Captopril; D011464:Epoprostenol; D009543:Nifedipine; D007213:Indomethacin