Effects of ioversol versus iothalamate on endothelin release and radiocontrast nephropathy.
OBJECTIVE
Certain radiocontrast agents, including iothalamate, iohexol, and ioxaglate, release the renal vasoconstrictor peptide endothelin from vascular endothelium in a way that might contribute to radiocontrast nephropathy. The effects of the nonionic, low osmolar agent, ioversol, on endothelin release and renal function are investigated.


METHODS
Effects of ioversol were compared with equi-iodine doses of iothalamate when applied to cultured bovine aortic endothelial cells or injected into normal rats and rats preconditioned by uninephrectomy, salt depletion, and indomethacin (USIC) to develop radiocontrast nephropathy.


RESULTS
In comparison with iothalamate, ioversol had a greatly reduced propensity to stimulate the release of endothelin, from cultured cells and when injected into anesthetized rats. Ioversol produced less renal vasoconstriction than did iothalamate, in control and in USIC rats, and the development of radiocontrast nephropathy, assessed by creatinine clearance and morphologic damage to the renal medulla, was largely avoided.


CONCLUSIONS
These results strengthen the hypothesis that endothelin release induced by radiocontrast agents is correlated with their renal toxicity and therefore, may play a role in radiocontrast nephropathy.
Heyman
S N
SN
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Clark
B A
BA
Cantley
L
L
Spokes
K
K
Rosen
S
S
Brezis
M
M
Epstein
F H
FH
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003287:Contrast Media / Q000009:adverse effects*; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007483:Iothalamic Acid / Q000009:adverse effects*; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D014283:Triiodobenzoic Acids / Q000009:adverse effects*
D003287:Contrast Media; D016232:Endothelins; D014283:Triiodobenzoic Acids; D007483:Iothalamic Acid; C054871:ioversol; D007213:Indomethacin