Chuanxiongzine relaxes isolated corpus cavernosum strips and raises intracavernous pressure in rabbits

Abstract

It has been shown that there are many Chinese traditional herbals that can enhance sexual activity. Chuanxiongzine is a vasoactive ingredient that has been isolated and purified from Ligusticum chuanxiong Hort. In previous studies, it has been found that chuanxiongzine was effective in relaxing rabbit corpus cavernosum smooth muscle. We determined the effects of chuanxiongzine on relaxation of isolated corpus cavernosum strips in vitro and on increase of intracavernous pressure (ICP) in vivo in rabbits. Chuanxiongzine caused a concentration-dependent relaxation of phenylephrine precontracted isolated corpus cavernosum strips (EC(50) 1.58 x 10(-4) mol l(-1)), which were endothelium independent and NO independent. However, the guanylyl cyclase inhibitor 1-H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one significantly shifted the chuanxiongzine concentration-response relationship to the right. Although there was no significant difference in the level of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) in isolated corpus cavernosum strips treated with chuanxiongzine or vehicle, chuanxiongzine caused a significant rise in the level of cGMP and cAMP in isolated corpus cavernosum strips pretreated with the activator of adenylyl cyclase forskolin and the source of NO sodium nitroprusside. In an in vivo study, chuanxiongzine dose-dependently raised ICP after the intracavernous injection of its cumulative doses (0.5, 1, 2 and 5 mg kg(-1)). The ICP increased from baseline to 19.1+/-3.7, 24.8+/-2.1, 30.2+/-4.8 and 39.7+/-6.1 mm Hg, respectively, and the duration of tumescence ranged from 8.5+/-2.8 to 22.9+/-7.3 min. Our results show that chuanxiongzine can relax isolated corpus cavernosum strips of rabbits in vitro and increase ICP of rabbits in vivo, which is neither endothelium dependent nor NO dependent, but may be partly mediated by the inhibition of cAMP phosphodiesterase or cGMP phosphodiesterase.

Figure 1

Chuanxiongzine-induced relaxation in isolated corpus cavernosum strips precontracted with 10⁻⁵ mol l⁻¹ phenylephrine. Symbols are mean±s.e.m. ^*P<0.05, when compared with that by the vehicle.

Figure 2

Effects of L-NAME (N^G-nitro-L-arginine methyl ester, 10⁻⁴ mol l⁻¹), ODQ (1-H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one, 10⁻⁴ mol l⁻¹) and removal of endothelium on chuanxiongzine-induced relaxation of isolated corpus cavernosum strips precontracted with phenylephrine (10⁻⁵ mol l⁻¹). Symbols are mean±s.e.m. ^*P<0.05, when compared with L-NAME and removal of endothelium.

Figure 3

(a) Effects of chuanxiongzine on the levels of cyclic adenosine monophosphate (cAMP) in isolated corpus cavernosum strips precontracted with phenylephrine and pretreated with forskolin and sodium nitroprusside. ^*P<0.05, when compared with control. (b) Effects of chuanxiongzine on the levels of cyclic guanosine monophosphate (cGMP) in isolated corpus cavernosum strips precontracted with PE and pretreated with forskolin and sodium nitroprusside. ^*P<0.05, when compared with control.

Figure 4

Chuanxiongzine-induced increase of ICP in rabbits. Symbols are mean±s.e.m., ICP: intracavernous pressure, SAP: systolic arterial pressure.