A comparative study of sildenafil, NCX-911 and BAY41-2272 on the anococcygeus muscle of diabetic rats.
We compared the effects of a nitric oxide (NO)-releasing sildenafil (NCX-911), NO-independent soluble guanylate cyclase activator (BAY41-2272) and sildenafil on the anococcygeus muscle from streptozotocin-induced 16-weeks diabetic rats. NCX-911, BAY41-2272 and sildenafil reduced the phenylephrine-induced tone in the control group (EC50=1088.8+/-165.0, 151.6+/-9.3 and 827.1+/-167.3 nM, respectively). The potencies of NCX-911 and BAY41-2272 were not altered, but that of sildenafil was significantly reduced in the diabetic group. EC50 values for NCX-911, BAY41-2272 and sildenafil in the diabetic group were 1765.9+/-303.5, 209.7+/-27.3 and 2842.2+/-640.3 nM, respectively (P<0.05 for sildenafil). Nitrergic relaxation responses were significantly decreased in the diabetic group. The remaining nitrergic relaxation responses were potentiated by BAY41-2272 but not by sildenafil or NCX-911. These results confirm that endogenous NO derived from nitrergic nerves is significantly decreased in diabetes, and suggest that NO-releasing PDE5 inhibitors and NO-independent soluble guanylate cyclase activators could be more useful than PDE5 inhibitors in the treatment of ED in long-term diabetes.
Kalsi
Jasjit S
JS
Wolfson Institute for Biomedical Research, University College London, Gower Street, Cruciform Building, London, UK.
Ralph
David J
DJ
Madge
David J
DJ
Kell
Phil D
PD
Cellek
Selim
S
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D001003:Anal Canal; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009132:Muscles / Q000187:drug effects* / Q000294:innervation; D026602:Nitrergic Neurons / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012445:Sacrococcygeal Region; D000068677:Sildenafil Citrate; D013450:Sulfones
C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; D000316:Adrenergic alpha-Agonists; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011720:Pyrazoles; D011725:Pyridines; D013450:Sulfones; D010656:Phenylephrine; D000068677:Sildenafil Citrate