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The relaxation effect and mechanism of action of higenamine in the rat corpus cavernosum

International Journal of Impotence Research volume 24, pages 77–83 (2012)Cite this article

Abstract

Higenamine mediates cardiotonic, vascular relaxation and bronchodilator effects. The relaxation effects and the mechanism of action of higenamine on the rat corpus cavernosum (CC) were assessed to investigate the effect of higenamine on penile erection. Strips of CC and aorta were used in organ baths for isometric tension studies. Tension was measured with isometric force transducers, and muscle relaxation was expressed as the percent decrease in precontraction induced by phenylephrine (PE). The relaxation reactions were investigated in an endothelial-denuded group and groups pretreated with N(G)-nitro-L-arginine methyl ester (NO synthesis inhibitor), propranolol (β-receptor blocker), indomethacin (COX inhibitor), glibenclamide (K+ATP channel inhibitor), 4-aminopyridine (membrane potential-dependent potassium channel inhibitor) and methylene blue (guanylyl cyclase inhibitor) for 30 min. Intracavernous pressure (ICP) was assessed in rats after the intravenous administration of higenamine, and changes in guanosine 3′,5′-cyclic monophosphate and adenosine 3′,5′-cyclic monophosphate (cAMP) concentrations were measured on the basis of the higenamine concentration. Also, the combined reaction of higenamine and the phosphodiesterase type-5 (PDE-5) inhibitors was assessed. Higenamine induced relaxation of the CC and the aortic strips precontracted with PE in a dose-dependent manner. The CC was significantly more relaxed than the aortic rings in response to the same higenamine concentration (P<0.05). The CC relaxation reaction was suppressed by the β-receptor blocker propranolol. The cAMP concentration increased gradually with increased higenamine concentration (P<0.05). The ICP also increased with increased higenamine concentration in vivo (P<0.05). In the group pretreated with 10−7 M higenamine, the relaxation reaction of CC induced by the PDE-5 inhibitor increased significantly, compared with CC exposed to the PDE-5 inhibitor but not pretreated with higenamine (P<0.05). In conclusion, higenamine induced relaxation of the rat CC in a dose-dependent manner. The effect may be mediated through β-adrenoceptors. The results suggest that higenamine may be valuable as a new lead compound for treating erectile dysfunction.

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Acknowledgements

This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (Ministry of Education, Science and Technology; NRF-2009-0067889 and 2010-0017131).

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Authors and Affiliations

  1. Department of Urology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea

    S C Kam, J M Do, J H Choi & J S Hyun

  2. Department of Anatomy, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea

    B T Jeon & G S Roh

  3. Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea

    K C Chang

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Correspondence to J S Hyun.

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Kam, S., Do, J., Choi, J. et al. The relaxation effect and mechanism of action of higenamine in the rat corpus cavernosum. Int J Impot Res 24, 77–83 (2012). https://doi.org/10.1038/ijir.2011.48

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