Et-A receptor antagonist BQ123 prevents radiocontrast media-induced renal medullary hypoxia.
OBJECTIVE
Renal vasoconstriction with resultant tissue hypoxia, especially in the renal medulla, has been suggested to play a role in contrast media (CM)-induced nephropathy. Endothelin (ET) is released into the blood stream following CM injection and has been proposed as a potential mediator through its vasoconstrictive properties.


METHODS
To investigate the possible protective influence of ET-receptor antagonists against CM-induced reduction in renal function, we studied the effects of injection of iopromide with and without pretreatment with BQ123 (ET-A antagonist) or BQ788 (ET-B antagonist) on renal superficial cortical flow (CBF), outer medullary blood flow (OMBF) and outer medullary oxygen tension (pO2) in normal rats.


RESULTS
Administration of CM (1600 mg I/kg b.w.) did not affect CBF in any of the groups. However, a transient decrease in OMBF occurred, which was unaffected by both BQ123 and BQ788. Also a transient decrease in outer medullary pO2 was induced by CM administration. The pO2 reduction was significantly smaller after pretreatment with BQ123, than after injection of CM alone or together with BQ788, and pO2 returned more rapidly to the control level. Neither receptor antagonist had an effect on CM-mediated increases in electrolyte excretion.


CONCLUSIONS
In the normal rat, activation of ET-A receptors is partly involved in the depression of outer medullary pO2 caused by injection of iopromide. However, the decrease in OMBF after iopromide injection is not mediated by ET receptors. The beneficial effects of the ET-A receptor antagonist on CM-induced changes in outer medullary pO2 seem therefore not primarily mediated on the hemodynamic level but may rather involve tubular transport mechanisms.
Liss
P
P
Department of Diagnostic Radiology, Uppsala University, Uppsala, Sweden. per.liss@rtg.uas.lul.se
Carlsson
P-O
PO
Nygren
A
A
Palm
F
F
Hansell
P
P
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003287:Contrast Media / Q000009:adverse effects*; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D000860:Hypoxia / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D007472:Iohexol / Q000009:adverse effects* / Q000031:analogs & derivatives*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D007679:Kidney Medulla / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use*; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000627:therapeutic use*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D003287:Contrast Media; D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D017466:Receptors, Endothelin; D007472:Iohexol; C086539:BQ 788; C038192:iopromide; C072247:cyclo(Trp-Asp-Pro-Val-Leu)