The relaxation mechanisms of tetrandrine on the rabbit corpus cavernosum tissue in vitro

Abstract

The relaxation mechanisms of tetrandrine (Tet) on the rabbit corpus cavernosum tissue in vitro were investigated. Strips of rabbit corpus cavernosum were mounted in organ chambers. The effects of Tet were examined on isolated muscle strips pre-contracted with phenylephrine (PE) alone, in the presence of N ^W-nitro-L-arginine (LNNA, a nitric oxide synthase inhibitor), 1-H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one(ODQ, a guanylyl cyclase inhibitor), indomethacin (cyclooxygenase inhibitor), tetraethylammonium (TEA, Ca²⁺-activated K⁺ channel blocker), 4-aminopiridine (4-AP, voltage dependent K⁺ channel blocker) and glibenclamide (ATP sensitive K⁺channel blocker). The effects of Tet on KCl-induced contraction of isolated muscle strips were also investigated. The procedure of calcium absence–calcium addition was designed to observe the effect of Tet on the two components of the contractile responses to PE based on the source of Ca²⁺ (extracellular vs. intracellular). Corpus cavernosum strips showed relaxation in response to Tet (10⁻⁸ ∼ 10⁻³ mol L⁻¹) in a concentration-dependent manner with an IC₅₀ of 3.73 × 10⁻⁵ mol L⁻¹. However, they were not affected by LNNA, ODQ, indomethacin and K⁺-channel blockers. Tet (10 μmol L⁻¹, 30 μmol L⁻¹) concentration dependently reduced the maximal contraction response of isolated strips induced by KCl to (73.0 ± 3.8) and (41.5 ± 3.4)%, respectively (p < 0.01). In the procedure of calcium absence–calcium addition, Tet 100 μmol L⁻¹ inhibited both intracellular calcium-dependent and extracellular calcium-dependent contraction induced by PE (20 μmol L⁻¹) (p < 0.05). The inhibition ratios were (23.8 ± 7.1) and (40.7 ± 11.2)%, respectively. The results of the present study suggest that Tet possesses a relaxant effect on rabbit corpus cavernosum tissues, which is attributable to the inhibition of extracellular Ca²⁺ influx and the inhibition of release of intracellular-stored Ca²⁺, but not mediated by the release of nitric oxide, prostaglandins or by the activation of potassium channels.

Keywords:

• tetrandrine
• corpus cavernosum
• relaxation

Acknowledgements

The authors thank Professor Jia-Ling Wang for kindly supplying the Tet. The technical assistance from Drs Lin Qu and Qing Lv (Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China) is also greatly appreciated. This study was sponsored by the National Natural Science Foundation of China (No. 30471736) and China Postdoctoral Science Foundation (20070410176).