Effect of an Ethanol Extract of Scutellaria baicalensis on Relaxation in Corpus Cavernosum Smooth Muscle

Abstract

Aims of study. The aim of the present study was to investigate whether an ethanol extract of Scutellaria baicalensis (ESB) relaxes penile corpus cavernosum muscle in organ bath experiments. Materials and methods. Changes in tension of cavernous smooth muscle strips were determined by penile strip chamber model and in penile perfusion model. Isolated endothelium-intact rabbit corpus cavernosum was precontracted with phenylephrine (PE) and then treated with ESB. Results. ESB relaxed penile smooth muscle in a dose-dependent manner, and this was inhibited by pre-treatment with N(G)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide (NO) synthase inhibitor, and 1H-[1, 2, 4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ), a soluble guanylyl cyclase (sGC) inhibitor. ESB-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA), a nonselective K(+) channel blocker, and charybdotoxin, a selective Ca(2+)-dependent K(+) channel inhibitor. ESB increased the cGMP levels of rabbit corpus cavernosum in a concentration-dependent manner without changes in cAMP levels. In a perfusion model of penile tissue, ESB also relaxed penile corpus cavernosum smooth muscle in a dose-dependent manner. Conclusion. Taken together, these results suggest that ESB relaxed rabbit cavernous smooth muscle via the NO/cGMP system and Ca(2+)-sensitive K(+) channels in the corpus cavernosum.

Figure 1

Chemical structures of compounds 1–4 (a) and an HPLC chromatographic profile of the extract of S. baicalensis (b). The identity of the compounds was confirmed by coelution with authentic samples.

Figure 2

Effects of ESB on PE-precontracted endothelium-intact cavernosal smooth muscle strips. The vehicle treatment was 0.1% DMSO. Mean values ± S.E. (n = 7) are shown.

Figure 3

(a) Effects of 0.1 mM l-NAME and 10 μM ODQ on ESB-induced relaxation of rabbit cavernosal smooth muscle strips. (c), (d) Effects of ESB on cGMP and cAMP level in crude homogenates of rabbit corpus cavernosum tissues. (b) Effects of l-NAME and ODQ on the ESB-induced increase of cGMP levels in crude homogenates of rabbit corpus cavernosum tissues. Mean values ± S.E. (n = 5) are shown. *P < 0.01, **P < 0.001 versus vehicle, ^# P < 0.001 versus ESB.

Figure 4

(a) Comparison of ESB-induced cavernous smooth muscle relaxation in high K-contracted and PE-precontracted rabbit cavernosum smooth muscle strips. The mean value ± S.E. are shown. KCl 45 mM (n = 5), KCl + ESB (n = 5), PE + ESB (n = 7). *P < 0.001 versus PE + ESB. (b) Effects of K⁺ channel blockade on ESB-induced rabbit cavernous smooth muscle relaxation. TEA, tetraethylammonium; gliben, glibenclamide. (c) Effect of K⁺-selective inhibitor on ESB-induced rabbit cavernous smooth muscle relaxation. Mean values ± S.E. (n = 5) is shown. *P < 0.001 versus vehicle. (d) Effect of 4-aminopyridine (4-AP) on ESB-induced rabbit cavernous smooth muscle relaxation. Mean values ± S.E. (n = 4) are shown.

Figure 5

Effect of 10 μM diltiazem on ESB-induced relaxation in PE-precontracted cavernosal smooth muscle strips. Mean values ± S.E. (n = 4) are shown.

Figure 6

Effect of 10 μM indomethacin, 1 μM atropine, and 1 μM propranolol on ESB-induced relaxation in PE-precontracted rabbit cavernosal smooth muscle strips. Mean values ± S.E. (n = 4) are shown.

Figure 7

(a) Effect of SNP (a), sildenafil (b), and ESB (c) on corpus cavernosum smooth muscle tension in the perfused rabbit penile tissue. Each value shows mean ± S.E. (n = 6). *P < 0.05, **P < 0.01, ***P < 0.001 versus PE.