Ushiyama Masayuki, Kuramochi Tomoya, Katayama Shigehiro
Fourth Department of Internal Medicine, Saitama Medical School, Saitama, Japan.
Hypertens Res. 2006 Jul;29(7):523-32. doi: 10.1291/hypres.29.523.
Treatment of erectile dysfunction (ED) in hypertensive subjects remains to be formally established. There is currently no standardized treatment for ED in hypertensive subjects. In this study, we tested our hypothesis that hypotensive drugs would improve impaired relaxation in the corpus cavernosum of spontaneously hypertensive rats (SHR). Ten-week-old SHR was treated with amlodipine, imidapril or hydralazine for 4 weeks. Although all three drugs achieved an equivalent decrease in systolic blood pressure (SBP), only amlodipine and imidapril induced an increase in relaxation in response to electrical field stimulation (EFS) of the corpus cavernosum. In the case of amlodipine, this effect was dose- and SBP-dependent. Nitric oxide (NO)-dependent relaxation was increased by amlodipine over a wide range of EFS frequencies, was increased by imidapril at low EFS frequencies, and was decreased by hydralazine. Carbon monoxide (CO)-dependent relaxation was only increased by hydralazine, and this increase occurred over a wide range of frequencies. The NOx and cGMP levels in the EFS-stimulated corpus cavernosum were increased by amlodipine. Amlodipine did not affect the thiobarbituric acid-reacting substance levels in the serum and the corpus cavernosum, but did decrease superoxide dismutase activity in the tissue. Imidapril and hydralazine inhibited the acetylcholine-induced relaxation in the corpus cavernosum. Sodium nitroprusside-induced relaxation in the tissue was increased by amlodipine. All three agents similarly inhibited the phenylephrine-induced contraction. These results suggest that impaired neurogenic relaxation in the corpus cavernosum of SHR is improved by amlodipine and imidapril through an increase in the synthesis and/or release of neuronal NO, but not CO, and presumably the inhibited detumescence of erection, which is induced by norepinephrine being released from sympathetic neuron. These findings indicate that amlodipine and imidapril may ameliorate the decreased relaxation of cavernous smooth muscle in the setting of hypertension.
高血压患者勃起功能障碍（ED）的治疗方法仍有待正式确立。目前，高血压患者的ED尚无标准化治疗方案。在本研究中，我们检验了以下假设：降压药物可改善自发性高血压大鼠（SHR）海绵体内受损的舒张功能。将10周龄的SHR用氨氯地平、咪达普利或肼屈嗪治疗4周。尽管这三种药物均可使收缩压（SBP）同等程度降低，但只有氨氯地平和咪达普利可使海绵体对电场刺激（EFS）的舒张反应增强。就氨氯地平而言，这种作用呈剂量和SBP依赖性。在较宽的EFS频率范围内，氨氯地平可增强一氧化氮（NO）依赖性舒张，咪达普利在低EFS频率时可增强该舒张，而肼屈嗪则使其降低。一氧化碳（CO）依赖性舒张仅在肼屈嗪作用下增强，且在较宽频率范围内均有此作用。氨氯地平可使EFS刺激的海绵体内NOx和cGMP水平升高。氨氯地平不影响血清和海绵体内硫代巴比妥酸反应物质水平，但可降低组织中超氧化物歧化酶活性。咪达普利和肼屈嗪可抑制海绵体内乙酰胆碱诱导的舒张。氨氯地平可增强硝普钠诱导的组织舒张。这三种药物均同样抑制去氧肾上腺素诱导的收缩。这些结果表明，氨氯地平和咪达普利可通过增加神经元NO而非CO的合成和/或释放，改善SHR海绵体内受损的神经源性舒张，推测可抑制由交感神经元释放的去甲肾上腺素诱导的勃起消退。这些发现提示，氨氯地平和咪达普利可能改善高血压状态下海绵体平滑肌舒张功能降低的情况。
