Improvement of Endothelial Function of the Corpus Cavernosum in Apolipoprotein E Knockout Mice Treated with Irbesartan
Improvement of Endothelial Function of the Corpus Cavernosum in Apolipoprotein E Knockout Mice Treated with Irbesartan
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DOI：
10.1124/jpet.108.140533
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发表时间：
2008-12-01
影响因子：
3.5
通讯作者：
Boehm, Michael
中科院分区：
文献类型：
--
作者：
Baumhaekel, Magnus;Custodis, Florian;Boehm, Michael
血管紧张素受体阻滞剂增强内皮功能，并建议改善勃起功能。在载脂蛋白E（ApoE）（-/-）小鼠中，测定血管紧张素受体阻滞剂厄贝沙坦对阴茎内皮功能的影响和潜在机制。野生型（C57/B6）和ApoE（-/-）小鼠用高脂肪、富含胆固醇的饮食喂养7周，并用厄贝沙坦（50 mg/kg.day）或肼苯哒嗪（250 mg/l）治疗。采用尾套法测量重要参数。在器官浴室中通过药理学刺激评估内皮（主动脉环）和勃起功能（海绵体）。测定氧化应激和血管紧张素受体表达。与对照组和野生型小鼠相比，厄贝沙坦和肼苯哒嗪治疗的ApoE（-/-）小鼠的血压显著降低（p < 0.05）。ApoE（-/-）小鼠的主动脉和阴茎海绵体内皮功能显著受损（p < 0.05），经厄贝沙坦治疗后可恢复（p < 0.05）。同样，ApoE（-/-）小鼠阴茎海绵体的一氧化氮产生受损（p < 0.01），厄贝沙坦治疗小鼠恢复，但肼屈嗪治疗小鼠未恢复。二氢乙锭染色切片和脂质过氧化物酶测定显示，与肼苯哒嗪处理和对照ApoE（-/-）小鼠相比，厄贝沙坦（p < 0.05）的超氧化物生成减少。总之，厄贝沙坦通过降低血管和海绵体氧化应激改善ApoE（-/-）小鼠的阴茎内皮功能。这一结果强调了抑制肾素-血管紧张素系统的有益作用，即使在勃起功能方面。
Angiotensin receptor blockers enhance endothelial function and are suggested to improve erectile function. The effects and underlying mechanisms of treatment with the angiotensin receptor blocker irbesartan on penile endothelial function in apolipoprotein E (ApoE)(-/-) mice were determined. Wild-type (C57/B6) and ApoE(-/-) mice were fed with a high-fat, cholesterol-rich diet for 7 weeks and treated with irbesartan (50 mg/kg.day) or hydralazine (250 mg/l). Vital parameters were measured with the tail-cuff method. Endothelial (aortic rings) and erectile function (corpora cavernosa) were assessed by pharmacological stimulation in an organ bath chamber. Oxidative stress and angiotensin receptor expression were determined. Blood pressure was significantly decreased in irbesartan- and hydralazine-treated ApoE(-/-) mice (p < 0.05) compared with controls and wild-type mice. Endothelial function of the aorta and corpus cavernosum was significantly impaired in ApoE(-/-) mice (p < 0.05) and could be restored by treatment with irbesartan (p < 0.05). Consistently, nitric oxide production of corpora cavernosa was impaired in ApoE(-/-) mice (p < 0.01), with a restoration in irbesartan- but not hydralazine-treated mice. Dihydroethidium-stained sections and lipid peroxidase assay revealed a reduction of superoxide production in irbesartan (p < 0.05) compared with hydralazine-treated and control ApoE(-/-) mice. In summary, irbesartan improves penile endothelial function in ApoE(-/-) mice by reduction of vascular and cavernosal oxidative stress. This result emphasizes the beneficial effect of inhibition of the renin- angiotensin system even in terms of erectile function.