Prevention of contrast medium-induced renal vasospasm by phosphodiesterase inhibition.

RATIONALE AND OBJECTIVES: 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.

Histamine release and contrast media-induced renal vasoconstriction.

RATIONALE AND OBJECTIVES: The authors' purpose was to investigate the role of histamine release causing renal vasoconstriction induced by application of contrast media, an important element in contrast medium-induced nephrotoxicity. MATERIALS AND METHODS: Isometric contractions in rabbit segmental renal arteries stimulated with KCl and increasing concentrations of the ionic contrast medium diatrizoate and the nonionic agents iomeprol and iodixanol were studied both with and without increasing concentrations of the histamine H1 and H2 blockers diphenhydramine and cimetidine. Histamine concentrations after contrast medium application were determined. RESULTS: Contrast-induced, dose-dependent, reversible renal artery contractions of 27%, 4.5%, and 5% of the control KCl contraction were found for diatrizoate, iodixanol, and iomeprol respectively. Those induced by the ionic contrast medium were statistically significantly higher (P < .01). Contractions were partially inhibited by diphenhydramine (49%) but not by cimetidine. Significant elevation of histamine concentrations (P < .05) was detected only after stimulation with diatrizoate but not with nonionic agents. CONCLUSION: Ionic contrast medium induces histamine release leading to renal vasoconstriction, which can be partly blocked by H1 blockers. Histamine has no effect on renal vasospasm induced by nonionic contrast media.

Effect of contrast medium on corpus cavernosum smooth muscle.

RATIONALE AND OBJECTIVES: Changes in contractility of corpus cavernosum (CC) smooth muscle caused by radio contrast medium may result in misinterpretations of cavernosography used diagnostically in erectile dysfunction. METHODS: The authors investigated the direct effect of various contrast media on rabbit CC smooth muscle tissue strips in an in vitro model by adding contrast medium to the tissue in a perfusion bath and recording the resulting contractions. Glucose addition was used as control. RESULTS: Application of high-osmolar, ionic contrast medium diatrizoate-induced CC smooth muscle contractions of 57% of the control potassium chloride (124 mM) induced contractions. The low-osmolar (862 mOsm/kg) nonionic monomer contrast medium, iohexol, and the iso-osmolar (300 mOsm/kg) nonionic-dimer contrast medium, iodixanol, elicited contractions of 34% and 36% of the potassium chloride control contractions, respectively. High- and Iso-osmolar glucose solutions caused contractions of 51%, 38%, and 24% of the control, respectively. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) regulate CC smooth muscle contractions. These are influenced by different drugs including phosphodiesterases (PDEs), forskolin, and 3-morpholinsydnonimine hydrochloride (SIN-1). The nonspecific PDE inhibitors papaverine (0.1 mM) and theophylline (1 mM) reduced the contrast medium-induced contractions to 66% and 69%, respectively. The specific PDE inhibitor milrinone (0.1 mM) reduced the contractions to 69%; 0.1 mM forskolin and SIN-1 reduced the contractions to 34% and 41%, respectively. CONCLUSIONS: Contrast medium induces CC smooth muscle contractions, depending mainly on the osmolality of the solution. The contractions are reduced but not abolished by elevating the intracellular cAMP and cGMP concentrations. The clinical applications in cavernosography are discussed.

Comparison of iodinated contrast media-induced renal vasoconstriction in human, rabbit, dog, and pig arteries.

RATIONALE AND OBJECTIVES: Contrast media (CM)-induced renal vasoconstriction is an important factor in the pathogenesis of CM-induced nephrotoxicity. The effects of ionic, high-osmolar CM sodium/meglumine diatrizoate and nonionic, low-osmolar CM iohexol and iopamidol were studied in rabbit, dog, and pig renal arteries and compared with human tissue in an organ bath. METHODS: Isometric contractions were induced by increasing concentrations of CM and high-osmolar glucose solution. RESULTS: Contrast media and glucose elicited contractions in human renal arteries of 32% (diatrizoate), 20% (iohexol), 30% (iopamidol), and 22% (glucose). Rabbit and dog renal arteries demonstrated contractions of 30% and 46% (diatrizoate), 15% and 23% (iohexol), 15% and 26% (iopamidol), and 11% and 40% (glucose), respectively, of the control. There was a vasorelaxing effect of all CM tested on pig renal artery. CONCLUSIONS: Responses in rabbit and dog renal arteries were similar to those in human renal arteries and could serve as models for investigating CM-induced renal vasoconstriction.

Variable effects of iodinated contrast media on different rabbit arteries in vitro.

Vasoconstriction caused by iodinated contrast media (CM) has been considered specific for the renal artery only. We examined the vascular effect of CM in rabbit carotid, aorta, renal, iliac, mesenteric and celiac arteries and found that other arteries also respond with a contraction to CM. Isolated arterial rings were exposed to diatrizoate (high osmolar CM), iohexol (low osmolar CM) or glucose solution, and the isometric contraction response was expressed as percentage of an initial KCl control contraction. Diatrizoate evoked contractions of 82% (carotid), 63% (aorta), 30% (renal), 24% (iliac), 28% (mesenteric) and 18% (celiac), respectively. Iohexol caused contractions of 31% (carotid), 24% (aorta), 15% (renal) and 14% (iliac), whereas the mesenteric and celiac arteries were relaxed by iohexol. A high osmolar glucose solution elicited contractions of 78%, 77%, 11%, 27%, 3% and 5%, respectively, in the arteries. CM have contraction potency in arterial vasculature other than the renal artery.

Transurethral resection versus incision of the prostate: a randomized, prospective study.

OBJECTIVES: To evaluate longer term effects of transurethral resection (TURP) and incision (TUIP) of the prostate in randomized patients. METHODS: In a randomized, prospective study, 120 patients with symptoms of bladder outlet obstruction caused by smaller benign prostates (estimated resectable weight less than 20 g) were assigned to TURP or TUIP. Patients were evaluated preoperatively and at intervals postoperatively as to urinary symptoms (Madsen's questionnaire), sexual function, and uroflowmetry. Overall evaluation of outcome of surgery was also assessed at follow-up visits. RESULTS: Fifty-six patients received a TURP and 61 a TUIP. Three patients refused to participate in the project after randomization, and 5 patients were lost to or excluded from follow-up. A group of 112 patients were obtainable for postoperative evaluation with a mean follow-up time of 34 months (1 to 82 months). Improvements in mean urinary peak flow rates were seen in both groups throughout the study period. The peak flow rates generally were higher (but not statistically so) in the TURP group. Postoperative irritative, obstructive, as well as total symptom scores decreased significantly at all follow-up visits after both TURP and TUIP (P < or = 0.034). Preoperatively and at all postoperative follow-up there was no statistically significant difference in irritative, obstructive, or total symptom scores between TURP and TUIP. The patients indicated an overall subjective improvement at all follow-ups in both groups, with no statistically significant difference between the treatment groups. Fifteen of 22 (68%) patients receiving TURP and 8 of 23 (35%) in the TUIP group who were sexually active before and after surgery developed postoperative retrograde ejaculation (P = 0.020). Postoperatively, 9 (16%) of the patients in the TURP and 14 (23%) in the TUIP group received further treatment for benign prostatic hyperplasia (BPH)-related infravesical obstruction. This difference was not statistically significant (P = 0.908). CONCLUSIONS: In small prostates TURP and TUIP were generally equally effective in relieving bladder outlet obstruction secondary to BPH. Most surgically treated BPH cases can be well managed by the incision technique, which is an underutilized procedure.

Contrast medium induced renal vasoconstriction, role of alpha receptors.

Standard imaging techniques for evaluation of renal and renovascular disease require the application of radiocontrast medium. The use of high osmolar, ionic radio contrast medium is however associated with adverse effects including acute renal insufficiency. Renal vasoconstriction seems to play an important role in the pathomechanism of this side effect. The cellular mechanisms however remain unsolved. Alpha 1-adrenoceptors and their subtypes are the crucial link between sympathetic stimulation and renal vasoconstriction. We investigated the role of alpha 1-receptors and the alpha 1A and alpha 1B subtypes in the renal artery and in sodium/meglumine diatrizoate induced renal artery smooth muscle contraction. Alpha 1-receptor induced rabbit renal artery contraction was produced by stimulation with the specific agonist phenylephrine which was antagonized dose-dependently and reversibly by the alpha 1-blockers prazosin, terazosin and YM 617. The alpha 1A-receptor was the prevalent receptor subtype in rabbit renal artery. This was identified by applying the specific alpha 1A-receptor antagonist 5-methylurapidil and the irreversible alpha 1B-receptor antagonist chloroethyllonidine. These two inhibited the PE induced contraction by 96% and 66%, respectively. Sodium/meglumine diatrizoate elicited renal artery contraction at 25% of the phenylephrine control. This contraction was not influenced by alpha 1-blockers indicating the absence of an alpha 1-receptor mediated process.