Liu S P, Hass M A, Horan P, Levin R M
Division of Basic and Pharmaceutical Sciences, Albany College of Pharmacy, N.Y. 12208, USA.
Pharmacology. 1998 Mar;56(3):144-9. doi: 10.1159/000028192.
When the penis is in the flaccid state, the corpus cavernosum smooth muscle is under adrenergic control in order to maintain the sinusoids in a contracted condition (primarily via alpha-adrenergic stimulation). Penile erection is mediated by relaxation of corporal smooth muscle through a variety of direct and indirect mechanisms. Pharmacological agents that either inhibit alpha-adrenergic transmission or facilitate corporal smooth muscle relaxation will be beneficial for penile erection. Preliminary studies on macrocycle 1, a novel bioactive agent, demonstrated that this compound inhibits receptor-stimulated contraction without significantly altering field-stimulated contraction. The current study was designed to determine the physiological effects of macrocycle 1 on the response of the rabbit corpus cavernosum to various forms of stimulation. Sexually mature male New Zealand White rabbits were used in this study. The corpus cavernosum was dissected sharply from the removed penis and two longitudinal strips were prepared for isometric tension studies. Each strip was prestimulated with 200 mumol/l phenylephrine to produce a maximal contraction. The influences of macrocycle 1 (15.6, 62.5, 250, 1,000 mumol/l) on both the contractile response to phenylephrine and the relaxant effects of field stimulation, carbachol, ATP and nitroprusside were determined. The results demonstrated that although basal tension was not altered, the contractile response to phenylephrine was decreased by 5, 18, 47 and 57%, respectively, by the different concentrations of macrocycle 1. The degree of relaxation induced by field stimulation of various frequencies was significantly enhanced by macrocycle 1 in a concentration-dependent manner. Similarly, the degrees of relaxation induced by bethanechol, ATP and nitroprusside were all significantly enhanced in a concentration-dependent manner. The conclusion from this study is that macrocycle 1 significantly inhibits phenylephrine-stimulated contraction and significantly enhances field-stimulated and pharmacologically induced relaxation. Although the mechanisms of action are not clear, its physiological effects on the rabbit corpus cavernosum implicate a potential for the treatment of erectile dysfunction.
当阴茎处于疲软状态时，海绵体平滑肌受肾上腺素能控制，以维持海绵窦处于收缩状态（主要通过α - 肾上腺素能刺激）。阴茎勃起是通过多种直接和间接机制使海绵体平滑肌松弛介导的。抑制α - 肾上腺素能传递或促进海绵体平滑肌松弛的药物对阴茎勃起有益。对新型生物活性剂大环化合物1的初步研究表明，该化合物可抑制受体刺激的收缩，而不会显著改变场刺激收缩。本研究旨在确定大环化合物1对兔海绵体对各种形式刺激反应的生理影响。本研究使用性成熟的雄性新西兰白兔。从切除的阴茎上锐性分离出海绵体，并制备两条纵向条带用于等长张力研究。每条条带先用200μmol/L去氧肾上腺素预刺激以产生最大收缩。测定大环化合物1（15.6、62.5、250、1000μmol/L）对去氧肾上腺素收缩反应以及场刺激、卡巴胆碱、ATP和硝普钠松弛作用的影响。结果表明，尽管基础张力未改变，但不同浓度的大环化合物1分别使去氧肾上腺素的收缩反应降低了5%、18%、47%和57%。大环化合物1以浓度依赖性方式显著增强了不同频率场刺激诱导的松弛程度。同样，氨甲酰甲胆碱、ATP和硝普钠诱导的松弛程度也均以浓度依赖性方式显著增强。本研究的结论是，大环化合物1显著抑制去氧肾上腺素刺激的收缩，并显著增强场刺激和药理诱导的松弛。尽管作用机制尚不清楚，但其对兔海绵体的生理作用提示其具有治疗勃起功能障碍的潜力。
