Effects of Crataegii fructus on the Contractile Response of Rabbit Corpus Cavernosum

산사(山査)가 토끼 음경해면체의 수축에 미치는 영향

  • Lee, Han Seok (Department of Physiology, College of Korean Medicine, Semyung University) ;
  • Park, Sun Young (Department of Physiology, College of Korean Medicine, Semyung University)
  • 이한석 (세명대학교 한의과대학 생리학교실) ;
  • 박선영 (세명대학교 한의과대학 생리학교실)
  • Received : 2013.06.14
  • Accepted : 2013.07.20
  • Published : 2013.10.25

Abstract

This study was aimed to evaluate the cavernosal relaxation effect of Crataegii fructus(CF) in the contracted rabbit penile corpus cavernosum by agonists.In order to study the effect of CF on the vasoconstriction of rabbit penile corpus cavernosum, isolated rabbit penile corpus cavernosum tissues were used for the experiment using organ baths containing Krebs solution.To investigate the cavernosal relaxation of CF, CF extract at $0.01{\sim}3.0mg/m{\ell}$ was added after penile corpus cavernosum were contracted by norepinephrine(NE) $1{\mu}M$. To analyze the mechanism of CF's vasorelaxation, CF extract infused into contracted penile tissues by NE after each treatment of indomethacin(IM), $N{\omega}$-nitro-L-arginine(L-NNA), methylene blue(MB), tetraethylammonium chloride(TEA).To study the effect of CF on influx of extracellular calcium chloride($Ca^{2+}$) in penile tissues, in $Ca^{2+}$-free krebs solution, $Ca^{2+}$ 1 mM infused into contracted penile tissues by NE after pretreatment of CF. Cytotoxic activity of CF on human umbilical vein endothelial cell(HUVEC) was measured by MTT assay, and nitric oxide(NO) prodution was measured by Griess reagent. CF relaxed cavernosal strip with endothelium contracted by NE, but in the strips without endothelium, CF-induced relaxation was significantly inhibited. The pretreatment of L-NNA, MB, TEA decreased significantly on the cavernosal relaxation than not-treatment of them. But the pretreatment of IM had no significant effect on the cavernosal relaxation. In $Ca^{2+}$-free krebs solution, when $Ca^{2+}$ infused into contracted penile tissues by NE, pretreatment of CF inhibit contraction induced by adding $Ca^{2+}$.NO production wasn't increased by treatment of CF on HUVEC. This findings showed that CF is effective for the relaxation of rabbit penile corpus cavernosum, and we suggest that CF relax rabbit corpus cavernosal smooth muscle through multiple action mechanisms that include increasing the release of nitric oxide from corporal sinusoidal endothelium, inhibition of $Ca^{2+}$ mobilization into cytosol from the extracellular fluid, and maybe a hyperpolarizing action.

Keywords

References

  1. 許浚. 東醫寶鑑. 서울, 南山堂, p 714, 1983.
  2. 김재길. 東洋天然藥物原色圖鑑. 서울, 영림사, pp 231-232, 1995.
  3. 신문예출판공사. 중약대사전. 신문예출판공사, pp 215-217, 1981.
  4. 李時珍. 本草綱目. 서울, 고문사, p 1014, 1980.
  5. 박성혜, 김영희, 전정우, 송유진, 한종현. Medicinal food로 활용하기 위한 산사에 관한연구(2)-산사발효액이 고지방식이에 있어 지질대사 개선에 미치는 기능성 평가-. 동의생리병리학회지 19(5):1272-1280, 2005.
  6. 손창우, 채종구, 김길훤, 신흥묵. 산사의 혈관이완 효능과 항산화 작용. 동의생리병리학회지 16(1):67-71, 2002.
  7. 유가량, 최호정, 김길훤, 신흥묵. 산사 Butanol 분획이 PGF2a-유도 혈관평활근 수축의 억제에 미치는 신호전달 연구. 동의생리병리학회지 17(2):461-466, 2003.
  8. 채종구, 김길훤, 신흥묵. 내피세포 nitric oxide 유리를 통한 산사의 혈관이완 작용. 동의생리병리학회지 17(1):146-150, 2003.
  9. 배명효, 김호현. 산사의 내피세포 의존성 혈관이완효과 기전에 대한 연구. 대한본초학회지 18(3):169-180, 2003.
  10. Park, S.W., Lee, C.H., Shin, D.H., Bang, N.S., Lee, S.M. Effect of SA1, a herbal formulation, on sexual behavior and penile erection. Biological and Pharmaceutical Bulletin 29(7):1383-1386, 2006. https://doi.org/10.1248/bpb.29.1383
  11. Lauralee Sherwood. 인체생리학. 서울, 라이프사이언스, pp 755-756, 2011.
  12. 최형기, 최영득, Adaikan P.G., Yu J. 발기부전환자에서의 홍삼의 효능에 관한 연구-동남아시아의 다국적 연구. 고려인삼학회지 23(4):247-256, 1999.
  13. Feelisch, M., Noack, E. Nitric oxide(NO) formation from nitrovasodilators occurs independently of hemoglobin ornon-heme iron. European Journal of Pharmacology 142: 465-469, 1987. https://doi.org/10.1016/0014-2999(87)90090-2
  14. Furchgott, R.F. Role of endothelium in responses of vascular smooth muscle. Circulation Research 53: 557-573, 1983. https://doi.org/10.1161/01.RES.53.5.557
  15. 이한석, 김호현, 신선미, 박선영. 山査가 토끼의 음경해면체의 수축에 미치는 영향. 세명대학교 한의학연구소 논문집 15: 17-34, 2012.
  16. Carmichael, J., DeGraff, W.G., Gazda,r A.F., Minna, J.D., Mitchell, J.B. Evaluation of a tetrazolium-based semiautomated colorimetric assay: Assessment of chemosensitivity testing. Cancer Research 47: 936-942, 1987.
  17. Tracey, W.R., Linden, J., Michae, I.J.P., Roger, A.J. Comparison of spectrophotometric and biological assay for nitric oxide and endothelium-derived relaxing factor(EDRF) : Neurospecificity of the diazotiazation reaction for NO and failure to detect EDRF. Journal of Pharmacology 252: 922-928, 1990.
  18. 신민교. 原色臨床本草學. 서울, 영림출판사, pp 421-422, 1992.
  19. 육창수, 現代本草學, 서울, 고문사, p 320, 1975.
  20. 고광재, 송용선. 산사추출액이 白鼠의 肥滿模型에 미치는 영향. 한국전통의학지 8(1):1-8, 1998.
  21. 왕수빈, 안은미, 정지욱. 기억력 감퇴모델에서 산사의 기억력 개선 효과에 관한 연구. 대한본초학회지 24(4):165-171, 2009.
  22. Christ, G.J. The penis as a vascular organ. Urologic Clinics of North America 22(4):727-745, 1995.
  23. 송봉근. 발기부전 치료의 한의학적 접근 방법에 관한 연구. 대한한의학학회지 17(2):74-76, 1996.
  24. Andersson, K.E., Wagner G. Physiology of penile erection. Physiology Research 75: 191-236, 1995.
  25. Wagner, G., Willis, E.A., Bro-Rasmussen, F., Nielsen, M.H. New theory on the mechanism of erection involving hitherto undescribed vessels. Lancet 20(1):416-418, 1982.
  26. Banya, Y., Ushiki, T., Takagane, H., Aoki, H., Kubo, T., Ohhori T., Die C. Two circulatory routes within the human corpus cavernosum penis: A scanning electron microscopic study of corrosion casts. Journal of Urology 142: 879-883, 1989. https://doi.org/10.1016/S0022-5347(17)38935-8
  27. Montorsi, F., Sarteschi, M., Maga, T., Guazzoni, G., Fabris, G.F., Rigatti, P., Pizzini, G., Miani, A. Functional anatomy of cavernous helicine arteries in potent subjects. Journal of Urology 159: 808-810, 1998. https://doi.org/10.1016/S0022-5347(01)63738-8
  28. FitzGerald, G.A., Smit,h B., Pedersen, A.K., Brach, A.R. Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation. The New England Journal of Medicine 310: 1065-1068, 1984. https://doi.org/10.1056/NEJM198404263101701
  29. Traish, A.M., Moreland, R.B., Huang, Y.H., Goldstein, I. Expression of functional alpha2-adrenergic receptor subtypes in human copus cavernosum and in cultured trabecular smooth muscle cells. Recept Signal Transduct 7: 55-67, 1997.
  30. Andersson, K.E., Erectile physiological and pathophysiological pathways involved in erectile dysfunction. Journal of Urology 170: 6-13, 2003.
  31. Stamler, J.S., Singel, D.J., Loscalzo, J. Biochemistry of nitric oxide and its redox activated forms. Science 258: 1898-1902, 1992. https://doi.org/10.1126/science.1281928
  32. Vanhoutte, P.M. Endothelial control of vasomotor function: from health to coronary disease. Circulation journal 67(7):572-575, 2003. https://doi.org/10.1253/circj.67.572
  33. Hecker, M. Endothelium-Derived Hyperpolarizing Factor-Fact or Fiction?. News in physiological sciences 15(1):1-5, 2000.
  34. Juliana, S.B., Cleber, E.T., Cristina, E.O., Fernanda, B.M.P., Renato, F., Edson, A., Gilberto, D.N. Relaxing effects induced by the soluble guanylyl cyclase stimulator BAY 41-2272 in human and rabbit corpus cavernosum. European Journal of Pharmacology 477: 163-169, 2003. https://doi.org/10.1016/j.ejphar.2003.08.012
  35. Gokce, G., Bagcivan I., Kilicarslan, H., Yildirim, S., Gultekin, Y.E., Sarioglu, Y. Relaxation effects of adrenomedullin in isolated rabbit corpus cavernosum smooth muscle. British Journal of International 93: 859-862, 2004. https://doi.org/10.1111/j.1464-410X.2003.04728.x
  36. Yang, Q., Shigemura, N., Underwood, M.J., Hsin, M., Xue, H.M., Huang, Y., He, G.W., Yu, C.M. NO and EDHF pathways in pulmonary arteries and veins are impaired in COPD patients. vascular pharmacology 57: 113-118, 2012. https://doi.org/10.1016/j.vph.2012.05.004
  37. Van der Zypp A., Majewski H. Effect of cGMP inhibitors on the actions of nitrodilators in rat aorta. Clinical and Experimental Pharmacology and Physiology 25: 38-43, 1998. https://doi.org/10.1111/j.1440-1681.1998.tb02141.x
  38. Ignarro, L.J. Biological actions and propeties of endothelium derived nitric oxide formaed and released from artery and vein. Circulation Research 65(1):1-21, 1989. https://doi.org/10.1161/01.RES.65.1.1
  39. Jin, L., Teixeira, C.E., Webb, R.C., Leite, R. Comparison of the involvement of protein kinase C in agonist-induced contractions in mouse aorta and corpus cavernosum. European Journal of Pharmacology 590: 363-368, 2008. https://doi.org/10.1016/j.ejphar.2008.06.001