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Relaxant responses to two Rho-kinase inhibitors, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632) and fasudil, were compared in the corpus cavernosum obtained from diabetic and non-diabetic mice. Streptozotocin (100 mg kg(-1) day(-1), for 2 days) induced diabetes with a blood glucose level of 318+/-55.4 mg dl(-1); whereas it was 85.4+/-4.1 mg dl(-1) in control mice (P0.05). Electrical field stimulation (40 V, 0.5 ms, 1, 2, 4, 8, 16 Hz for 15 s) and acetylcholine-induced relaxations were markedly attenuated in the corpus cavernosum from streptozotocin-diabetic mice whereas responses to Y-27632 (10(-9)-3 x 10(-5) M) and fasudil (10(-9)-3 x 10(-5) M) were not altered. EC(50) values for Y-27632 were 2.98+/-0.89 and 4.19+/-2.71 microM in the corpus cavernosum from control and diabetic mice, respectively (P0.05). The values for fasudil were 7.42+/-4.91 and 3.53+/-1.41 microM in the corpus cavernosum from control and diabetic mice, respectively (P0.05). These results may suggest that, in diabetes, the relaxant effects of the Rho-kinase inhibitors may not be changed and thus, they may have a beneficial therapeutic effect in diabetic erectile dysfunction.

Isolated rabbit corpus cavernosum relaxed in response to ultraviolet (UV) light (365 nm). The UV light-induced relaxation (photorelaxation) was diminished on repeated UV irradiation from 30.5 +/- 4.0% (the first photorelaxation) to 15.5 +/- 2.7% (the last photorelaxation). Hydroxocobolamine of 100 muM and hemoglobin (Hb) of 10 muM, which are nitric oxide (NO) scavengers, and 10 muM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a soluble guanylyl cyclase inhibitor, markedly reduced photorelaxation, However, 300 muM 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO) failed to inhibit photorelaxation. NaNO2 and N-G-nitro-L-arginine (L-NA) but not 3-nitro-L-tyrosine (3-NT),were found to be photosensitive in that these compounds are photolysed to release NO, as demonstrated by use of an amperometric NO probed NO signals produced by 500 muM NaNO2, and 500 muM L-NA were 133.3 +/- 28.9 and 54.4 +/- 10.4 pA, respectively, Not 3-NT but the other compounds (all 200 muM) also enhanced photorelaxation of the cavernosal tissue. Based on these findings, the substance, which mediates photorelaxation, could be NO released from putative stores in the rabbit corpus cavernosum, and L-NA as well as NaNO2 but not 3-NT produce NO under the influence of UV light. (C) 2002 Published by Elsevier Science B.V.