Prevention of contrast medium-induced renal vasospasm by phosphodiesterase inhibition.
OBJECTIVE
This study investigated the involvement of cyclic adenosine monophosphate (cAMP) in contrast medium-induced renal vasomotor effects and the efficacy of selective phosphodiesterase (PDE) inhibitors influencing cAMP in preventing contrast medium-induced renal vasospasm.


METHODS
Isometric contractions of rabbit renal artery rings were subjected to increasing concentrations of the ionic contrast medium sodium/meglumine diatrizoate (DIA) and the nonionic contrast media iopamidol (IOP) and iodixanol (IOD) and compared with a potassium chloride control. Subsequently increasing concentrations of the nonselective phosphodiesterase inhibitors theophylline and papaverine and the following selective phosphodiesterase inhibitors were applied: vinpocetine, trequinsin, zardaverine, rolipram, and dipyridamole (subtypes I-V) before restimulation of the arterial tissue with contrast medium.


RESULTS
Diatrizoate, iopamidol, and iodixanol induced contractions up to 30%, 15%, and 3.5% of the potassium chloride control, respectively. All phosphodiesterase inhibitors markedly inhibited the contrast medium-induced contractions in a dose-dependent manner. The selective phosphodiesterase inhibitors rolipram and trequinsin attenuated these contractions significantly more (92% and 94%) than did zardaverine, dipyridamole, and vinpocetine, with an inhibitory potency of 37%, 41%, and 62%, respectively.


CONCLUSIONS
Nonionic contrast media induced renal vasoconstriction less potently than ionic contrast media. Significant differences in the ability to prevent contrast medium-induced vasoconstriction were observed among the various phosphodiesterase subtypes studied. selective phosphodiesterase inhibition with inhibitor subtypes II and IV showed the most promising results in specifically preventing contrast medium-induced renal vasospasm.
Drescher
P
P
Department of Radiology, Medical College of Wisconsin, Milwaukee 53226, USA. drescher@post.its.mcw.edu
Knes
J M
JM
Madsen
P O
PO
D000818:Animals; D003287:Contrast Media / Q000009:adverse effects*; D003974:Diatrizoate Meglumine / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D007479:Iopamidol / Q000009:adverse effects*; D010276:Parasympatholytics / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects*; D013035:Spasm / Q000139:chemically induced / Q000517:prevention & control; D014283:Triiodobenzoic Acids / Q000009:adverse effects*; D014652:Vascular Diseases / Q000139:chemically induced / Q000517:prevention & control*; D014661:Vasoconstriction / Q000187:drug effects
D003287:Contrast Media; D010276:Parasympatholytics; D010726:Phosphodiesterase Inhibitors; D014283:Triiodobenzoic Acids; D003974:Diatrizoate Meglumine; C044834:iodixanol; D007479:Iopamidol