Effects of the Rho-kinase inhibitors, Y-27632 and fasudil, on the corpus cavernosum from diabetic mice

Relaxant responses to two Rho-kinase inhibitors, (+)-(R)-trans-4-(I-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 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 (P < 0.05). 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. EC50 values for Y-27632 were 2.98 +/- 0.89 and 4.19 +/- 2.71 mu M in the corpus cavernosum from control and diabetic mice, respectively (P > 0.05). The values for fasudil were 7.42 +/- 4.91 and 3.53 +/- 1.41 muM in the corpus cavernosum from control and diabetic mice, respectively (P > 0.05). 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. (C) 2003 Elsevier Science B.V. All rights reserved.