Mazza Osvaldo Néstor, Angerosa Margarita, Becher Edgardo, Toblli Jorge Eduardo
Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina.
Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina.
J Sex Med. 2006 Jul;3(4):604-611. doi: 10.1111/j.1743-6109.2006.00235.x.
Previous studies indicate that angiotensin type I receptor antagonists present a beneficial effect on penile structures in hypertensive rats. However, at present there is no substantial information concerning the functional aspect of this class of antihypertensive drugs.
To determine, by in vitro studies, functional effects of Candesartan in comparison with a traditional vasodilating agent, Hydralazine, on penile structures in a rat model of arterial hypertension.
During 4 months, three groups of male spontaneously hypertensive rats (SHR) and one of Wistar-Kyoto (WKY) rats, as control group, were studied: SHR without treatment; SHR with Candesartan cilexetil 7.5 mg/kg/day; SHR with Hydralazine 50 mg/kg/day; and WKY rats without treatment. Cavernous smooth muscle strips were mounted in an organ bath system for in vitro studies. In addition, cavernous smooth muscle and vascular smooth muscle from cavernous arteries, cavernous tissue fibrosis, and collagen type III were also evaluated by immunohistochemistry.
After 4 months, SHR with Candesartan and Hydralazine showed similar reduction in blood pressure compared with untreated SHR. However, in vitro studies revealed that SHR with Candesartan displayed a better relaxation response to acetylcholine than SHR and SHR with Hydralazine (P < 0.01). Immunostaining indicates that only SHR with Candesartan and control WKY rats showed significantly lower values of: (i) cavernous smooth muscle (P < 0.01); (ii) vascular smooth muscle (P < 0.01); and (iii) collagen type III (P < 0.01) when compared with untreated SHR or SHR with Hydralazine. Additionally, SHR with Candesartan presented a higher endothelial nitric oxide synthase expression in sinusoidal endothelium in comparison with SHR, and SHR with Hydralazine (P < 0.01).
Candesartan presented equivalent blood pressure control compared with Hydralazine. However, only Candesartan showed a significant better response to acetylcholine, in in vitro studies, with a protective role against structural changes in vessels as well as in cavernous spaces of the erectile tissue.
先前的研究表明，血管紧张素I型受体拮抗剂对高血压大鼠的阴茎结构具有有益作用。然而，目前关于这类抗高血压药物的功能方面尚无实质性信息。
通过体外研究，比较坎地沙坦与传统血管扩张剂肼屈嗪对动脉高血压大鼠模型阴茎结构的功能影响。
在4个月的时间里，研究了三组雄性自发性高血压大鼠（SHR）和一组作为对照组的Wistar-Kyoto（WKY）大鼠：未治疗的SHR；服用坎地沙坦西酯7.5毫克/千克/天的SHR；服用肼屈嗪50毫克/千克/天的SHR；以及未治疗的WKY大鼠。将海绵体平滑肌条安装在器官浴系统中进行体外研究。此外，还通过免疫组织化学评估了海绵体动脉的海绵体平滑肌和血管平滑肌、海绵体组织纤维化以及III型胶原蛋白。
4个月后，服用坎地沙坦和肼屈嗪的SHR与未治疗的SHR相比，血压下降程度相似。然而，体外研究表明，服用坎地沙坦的SHR对乙酰胆碱的舒张反应优于未治疗的SHR和服用肼屈嗪的SHR（P < 0.01）。免疫染色表明，与未治疗的SHR或服用肼屈嗪的SHR相比，只有服用坎地沙坦的SHR和对照WKY大鼠在以下方面的值显著较低：（i）海绵体平滑肌（P < 0.01）；（ii）血管平滑肌（P < 0.01）；（iii）III型胶原蛋白（P < 0.01）。此外，与未治疗的SHR和服用肼屈嗪的SHR相比，服用坎地沙坦的SHR在窦状内皮中的内皮型一氧化氮合酶表达更高（P < 0.01）。
与肼屈嗪相比，坎地沙坦在控制血压方面效果相当。然而，在体外研究中，只有坎地沙坦对乙酰胆碱表现出明显更好且对勃起组织血管及海绵体空间的结构变化具有保护作用的反应。
Zotero 插件