The effect of chronic renal failure on phosphodiesterase inhibitor-induced relaxation responses in rabbit cavernosal strips.
Erectile dysfunction is common in men with chronic renal failure. Previously nitrergic and endothelium-dependent relaxation responses have been shown to be reduced in chronic renal failure rabbits. We have therefore investigated the efficacy of phosphodiesterase inhibitors on the corpora cavernosa obtained from uremic rabbits. Uremia was induced with 5/6 nephrectomy and 4 weeks later cavernosal tissue strips were isolated. The relaxant effect of phosphodiesterase 5 inhibitors, zaprinast (1-300 microM) and sildenafil (0.01-300 microM), phosphodiesterase 3 inhibitor amrinone (1-100 microM) and non-specific phosphodiesterase inhibitor papaverine (1-300 microM) were investigated on phenylephrine (10 microM)-induced tone. We found a shift in the dose-response curve of only phosphodiesterase 5 inhibitors. These results suggest that the decreased production or availability of endogenous nitric oxide in chronic renal failure animals leads to decreased efficacy of phosphodiesterase 5 inhibitors to induce relaxation.
Kilicarslan
Hakan
H
Department of Urology, Faculty of Medicine, University of Cumhuriyet, 58140 Sivas, Turkey.
Yildirim
Sahin
S
Bagcivan
Ihsan
I
Gokce
Gokhan
G
Sarac
Bulent
B
Sarioglu
Yusuf
Y
D000676:Amrinone / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009392:Nephrectomy / Q000009:adverse effects; D010208:Papaverine / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000378:metabolism; D010413:Penis / Q000187:drug effects* / Q000502:physiology; D010710:Phosphates / Q000097:blood / Q000652:urine; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010740:Phospholipases / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000494:pharmacology; D011687:Purines; D011688:Purinones / Q000494:pharmacology; D011817:Rabbits; D000068677:Sildenafil Citrate; D013450:Sulfones; D013739:Testosterone / Q000378:metabolism
D007527:Isoenzymes; D010281:Parathyroid Hormone; D010710:Phosphates; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011688:Purinones; D013450:Sulfones; D013739:Testosterone; D003404:Creatinine; D000068677:Sildenafil Citrate; D010208:Papaverine; D010740:Phospholipases; C011145:zaprinast; D000676:Amrinone; D002118:Calcium