EFFECT OF RADIOGRAPHIC CONTRAST-MEDIA ON ENDOTHELIUM-DERIVED NITRIC OXIDE-DEPENDENT RENAL VASODILATATION

The effect of diatrizoate (Urografin325) on the cumulative dose-respon se curve of the vasodilatory response to acetylcholine was studied in the isolated perfused rat kidney (IPRK). The effect of 1-nitroarginine methyl ester (L-NAME) (10 mu mol l(-1)) on the cumulative concentrati on-response curve of the vasodilatory response to acetylcholine and so dium nitroprusside was also studied. Acetylcholine is a vasodilator de pendent on nitric oxide (NO) synthesis by the endothelium; sodium nitr oprusside is a vasodilator not dependent on endogenous NO synthesis an d L-NAME is an inhibitor of endogenous NO synthesis. The effect of L-N AME (10 mu mol l(-1)) on the vasodilatory effect of diatrizoate which is observed in the presence of endothelin A receptor antagonist (BQ123 , 10 mu mol l(-1)) was also studied. In all experiments an infusion of angiotensin II (5 ng min(-1)) was maintained to increase the vascular tone of the preparation. Acetylcholine induced vasodilatation and the maximum increase in renal perfusate flow (RPF) was 17.0+/-1.7%, (p<0. 05). Diatrizoate (20 mgI ml(-1) perfusate concentration) which induced a sustained fall in the RPF (- 31.0+/-1.7%, p<0.05) had no effect on the vasodilatory response to acetylcholine, and a similar increase in the RPF (17.8+/-2.2%, p<0.05) was observed. In contrast, L-NAME (10 mu mol l(-1)) completely abolished the vasodilatory effect of acetylchol ine and produced instead a modest decrease in RPF by -5.0+/-1.7% (p<0. 05). The vasodilatory effect of sodium nitroprusside was not affected by L-NAME, confirming its selectivity as an inhibitor of endogenous NO synthesis in the IPRK. The maximum increase in the RPF induced by sod ium nitroprusside was 23.1+/-2.0% (p<0.05) in the absence of L-NAME an d 21.2+/-2.2% (p<0.05) in its presence. L-NAME did not interfere with the vasodilatation induced by diatrizoate in the presence of BQ123. In the presence of BQ123 alone the RPF increased from 23.3+/-1.4 ml min( -1) g(-1) to 26.5+/-1.0 ml min(-1) g(-1) (p<0.05). In the presence of L-NAME and BQ123 the RPF increased from 24.4+/-3.0 ml min(-1) g(-1) to 27.2+/-2.7 ml min(-1) g(-1) (p < 0.05). There was no difference betwe en the two groups (p>0.05). In conclusion, diatrizoate did not interfe re with endothelium derived NO-dependent vasodilatation in the kidney. A reduced production of NO in the vascular endothelium induced by con trast media is unlikely to play any role in the pathophysiology of the increase in renal vascular resistance produced by these agents. The r enal vasodilatation induced by diatrizoate is not dependent on endogen ous production of NO.