Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, University of São Paulo (USP), Brazil.
BJU Int. 2010 Jun;105(11):1592-7. doi: 10.1111/j.1464-410X.2009.09084.x. Epub 2010 Feb 2.
To investigate the effects of chronic ethanol consumption and diabetes on nitric oxide (NO)-mediated relaxation of cavernosal smooth muscle (CSM).
Male Wistar rats were divided into four groups: control, isocaloric, diabetic and ethanol-diabetic. The CSMs were mounted in organ chambers for measurement of isometric tension. Contraction of the strips was induced by electrical field stimulation (EFS, 1-32 Hz) and phenylephrine. We also evaluated the effect of ethanol consumption on the relaxation induced by acetylcholine (ACh; 0.01-1000 micromol/L), sodium nitroprusside (SNP, 0.01-1000 micromol/L) or EFS (1-32 Hz) in strips pre-contracted with phenylephrine (10 micromol/L). Immunoexpression of endothelial NO synthase (eNOS) and inducible NOS (iNOS) was also accessed.
The endothelium-dependent relaxation induced by ACh was decreased in CSM from ethanol-diabetic rats when compared with the controls, with a mean (sem) of 21 (4) vs 37 (2)%. Similarly, the potency and maximal responses induced by SNP were reduced in the ethanol-diabetic [3.97 (0.38) and 85 (1)%, respectively] and diabetic groups [3.78 (0.56) and 81 (2)%, respectively] when compared with the controls [5.3 (0.22) and 90 (3)%, respectively] and isocaloric [5.3 (0.19) and 92 (1)%, respectively] groups. Noradrenergic nerve-mediated contractions of CSM in response to EFS were increased in rats from ethanol-diabetic and diabetic groups when compared with the control and isocaloric groups. Conversely, there were no differences in EFS-induced relaxation among the groups. The immunostaining assays showed overexpression of eNOS and iNOS in the CSM from diabetic and ethanol-diabetic rats when compared with the control and isocaloric rats.
There was an impairment of relaxation of CSM from ethanol-diabetic and diabetic rats that involved a decrease in the NO-cyclic guanosine monophosphate signalling pathway by endothelium-dependent mechanisms accompanied by a change in the CSM contractile sensitivity.
研究慢性乙醇摄入和糖尿病对海绵体平滑肌（CSM）中一氧化氮（NO）介导的松弛的影响。
雄性 Wistar 大鼠分为四组：对照组、等热量组、糖尿病组和乙醇糖尿病组。CSM 被安装在器官室中，用于测量等长张力。通过电场刺激（EFS，1-32 Hz）和苯肾上腺素诱导条带收缩。我们还评估了乙醇消耗对预先用苯肾上腺素（10 μmol/L）收缩的条带中乙酰胆碱（ACh；0.01-1000 μmol/L）、硝普钠（SNP，0.01-1000 μmol/L）或 EFS（1-32 Hz）诱导的松弛的影响。还评估了内皮型一氧化氮合酶（eNOS）和诱导型一氧化氮合酶（iNOS）的免疫表达。
与对照组相比，乙醇糖尿病大鼠 CSM 中由 ACh 诱导的内皮依赖性松弛减少，平均值（SEM）为 21（4）%与 37（2）%。同样，SNP 诱导的效力和最大反应在乙醇糖尿病[3.97（0.38）和 85（1）%，分别]和糖尿病组[3.78（0.56）和 81（2）%，分别]与对照组[5.3（0.22）和 90（3）%，分别]和等热量组[5.3（0.19）和 92（1）%，分别]相比降低。与对照组和等热量组相比，乙醇糖尿病和糖尿病大鼠 CSM 对 EFS 的去甲肾上腺素能神经介导收缩增加。相反，各组之间 EFS 诱导的松弛没有差异。免疫染色测定显示，与对照组和等热量组相比，糖尿病和乙醇糖尿病大鼠的 CSM 中 eNOS 和 iNOS 的表达过度。
乙醇糖尿病和糖尿病大鼠的 CSM 松弛受损，涉及内皮依赖性机制的 NO-环鸟苷酸信号通路减少，同时 CSM 收缩敏感性发生变化。
