Tong Y C, Wang C J, Chan P, Cheng J T
Department of Urology and Pharmacology, National Cheng Kung University Medical College, Tainan, Taiwan.
Urol Int. 2000;64(3):149-53. doi: 10.1159/000030516.
The effect of N-(biphenylyl-methyl)imidazole, losartan potassium, a newly developed antihypertensive type 1 angiotensin II receptor antagonist on the rat erectile function, was studied. Sexually active 9-week-old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were given losartan 60 mg/kg intraperitoneal injections. Mean blood pressure (MBP) dropped significantly in both SHR and WKY rats (for SHR: from 140 +/- 8 to 114 +/- 5 mm Hg, p < 0.05, n = 8; for WKY: from 113 +/- 7 to 79 +/- 9 mm Hg, p < 0.05, n = 8). On the contrary, the intracavernous pressure (ICP) of SHR and WKY rats did not differ significantly from that of the corresponding controls receiving saline injections (p > 0.05, n = 8 for each group). For the chronic study, the rats were fed with losartan 30 mg/kg/day for 30 days. MBP decreased significantly in SHR but not in WKY rats (for SHR: from 137 +/- 7 to 113 +/- 5 mm Hg, p < 0.05, n = 8; for WKY: from 110 +/- 6 to 107 +/- 5 mm Hg, p > 0.05, n = 8). The ICP of the losartan-treated rats was not significantly different from that of control rats (p > 0.05, n = 8 for each group). In contrast, WKY rats receiving guanethidine 1 mg/kg/day for 30 days showed significantly decreased ICP. Angiotensin II (10(-9)-10(-5) M) and losartan (10(-9)- 10(-5) M) did not induce significant contractile responses of the cavernosal strip when tested in vitro. On the other hand, methoxamine 10(-4) M induced good contractile responses. In conclusion, the present study demonstrated that angiotensin II did not cause significant change in the contractile status of rat corpus cavernosum. Correspondingly, the type 1 angiotensin II inhibitor effectively lowered blood pressure but did not affect cavernosal contractile function, thus is useful clinically in the treatment of hypertensive disorders without significant detrimental effects on male sexual function.
研究了新开发的抗高血压药物1型血管紧张素II受体拮抗剂洛沙坦钾（N-(联苯甲基)咪唑）对大鼠勃起功能的影响。对9周龄性活跃的雄性自发性高血压大鼠（SHR）和血压正常的Wistar-Kyoto（WKY）大鼠腹腔注射60mg/kg洛沙坦。SHR和WKY大鼠的平均血压（MBP）均显著下降（SHR：从140±8降至114±5mmHg，p<0.05，n = 8；WKY：从113±7降至79±9mmHg，p<0.05，n = 8）。相反，SHR和WKY大鼠的海绵体内压（ICP）与接受盐水注射的相应对照组相比无显著差异（p>0.05，每组n = 8）。在慢性研究中，给大鼠喂食30mg/kg/天的洛沙坦，持续30天。SHR大鼠的MBP显著下降，而WKY大鼠则未下降（SHR：从137±7降至113±5mmHg，p<0.05，n = 8；WKY：从110±6降至107±5mmHg，p>0.05，n = 8）。接受洛沙坦治疗的大鼠的ICP与对照大鼠无显著差异（p>0.05，每组n = 8）。相比之下，接受1mg/kg/天胍乙啶治疗30天的WKY大鼠的ICP显著下降。在体外测试时，血管紧张素II（10(-9)-10(-5)M）和洛沙坦（10(-9)-10(-5)M）未诱导海绵体条带产生显著的收缩反应。另一方面，10(-4)M的甲氧明诱导了良好的收缩反应。总之，本研究表明血管紧张素II不会引起大鼠海绵体收缩状态的显著变化。相应地，1型血管紧张素II抑制剂可有效降低血压，但不影响海绵体收缩功能，因此在临床上可用于治疗高血压疾病，而对男性性功能无明显有害影响。
