Gur Serap, Kadowitz Philip J, Thammasitboon Supat, Lasky Joseph A, Hellstrom Wayne J G
Departments of Urology and Pharmacology, Pulmonary and Critical Care Medicine, Tulane Health Sciences Center, New Orleans, Louisiana 70112, USA.
J Androl. 2009 Sep-Oct;30(5):495-504. doi: 10.2164/jandrol.108.006700. Epub 2009 Feb 5.
The aim of this study was to evaluate erectile function in monocrotaline (MCT)-treated rats with pulmonary hypertension (PH). Forty rats were divided into control (n = 20) and MCT-treated (n = 20) groups. Rats were treated with MCT (60 mg/kg subcutaneously) for 3 weeks to induce PH. Mean pulmonary arterial pressure (mPAP), medial hypertrophy index (percentage of wall thickness of pulmonary artery), and right ventricular hypertrophy (ratio of right ventricle [RV] to left ventricle + septum weight) were evaluated. In vivo erectile responses were assessed by measurement of intracavernosal pressure (ICP)/mean arterial pressure and total ICP (area under the curve). In vitro organ bath studies with corpus cavernosum smooth muscle strips were performed under both normoxic (95% O(2)/5% CO(2)) and hypoxic (by changing gas mixture to 95% N(2)/5% CO(2)) conditions. Erectile tissue was processed for immunohistochemistry. The MCT-treated group was associated with an increase in mPAP, medial hypertrophy index, and RV hypertrophy. MCT-induced PH rats had significantly reduced erectile responses compared with controls. Nitrergic, endothelium-dependent relaxations, as well as alpha-adrenergic contractile responses were significantly reduced in the corpus cavernosum of MCT rats. The functional responses during prolonged periods of hypoxia were similar to those observed in MCT-treated tissues. PH rats showed enhanced inducible nitric oxide synthase (NOS) protein localization, but endothelial NOS and neuronal NOS were unchanged. These results suggest changes in cavernosal physiology are caused by MCT acting on the penile tissues and the systemic vasculature.
本研究的目的是评估用野百合碱(MCT)治疗的肺动脉高压(PH)大鼠的勃起功能。40只大鼠被分为对照组(n = 20)和MCT治疗组(n = 20)。大鼠皮下注射MCT(60 mg/kg),持续3周以诱导PH。评估平均肺动脉压(mPAP)、中膜肥厚指数(肺动脉壁厚度百分比)和右心室肥厚(右心室[RV]与左心室+室间隔重量之比)。通过测量海绵体内压(ICP)/平均动脉压和总ICP(曲线下面积)评估体内勃起反应。在常氧(95% O₂/5% CO₂)和低氧(通过将气体混合物改为95% N₂/5% CO₂)条件下,对海绵体平滑肌条进行体外器官浴研究。对勃起组织进行免疫组织化学处理。MCT治疗组的mPAP、中膜肥厚指数和RV肥厚增加。与对照组相比,MCT诱导的PH大鼠的勃起反应显著降低。MCT大鼠海绵体内的一氧化氮能、内皮依赖性舒张以及α-肾上腺素能收缩反应均显著降低。长时间低氧期间的功能反应与MCT处理组织中观察到的反应相似。PH大鼠的诱导型一氧化氮合酶(NOS)蛋白定位增强,但内皮型NOS和神经元型NOS未改变。这些结果表明,海绵体生理变化是由MCT作用于阴茎组织和全身血管系统引起的。