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

摘要

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 (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. 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 (P>0.05). 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 (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.