Relaxation of corpus cavernosum and raised intracavernous pressure by berberine in rabbit

1 In the present study, we have investigated the effect of berberine in rabbit isolated corpus cavernosum and measured the intracavernous pressure (ICP) change after intracavernosal injection of berberine in rabbit. 2 Berberine alone suppressed the basal tone and induced a concentration (0.1-100 mu M)-dependent relaxation in phenylephrine (PE)-precontracted corpus cavernosum 3 Tetrodotoxin (0.1 and 1 mu M) treatment had no significant effect on the berberine-induced relaxation. Phentolamine (1 and 10 mu M), propranolol (1 and 3 mu M) and atropine (1 and 3 mu M) were also without effect. These results suggest that berberine might cause relaxation of the cavernosal strip by direct action on the corpus cavernosum, not by a neuronal effect. Furthermore, muscarinic- and beta-adrenoceptors were not involved. 4 Berberine-induced relaxations were significantly reduced by endothelium removal and by exposure to L-N-G-nitro arginine methyl ester (0.1 and 0.3 mM), but not indomethacin (30 mu M). 5 In endothelium-deprived corpus cavernosal tissues, berberine-induced relaxations were significantly reduced in high K+ medium (KCl=60 mM), by charybdotoxin (ChTX) and 4-aminopyridine (4-AP) but not by glibenclamide and apamin. 6 After intracavernous injection of berberine (1, 2, 3 and 5 mg kg(-1)), the ICP rose from 12.7+/-3.6 to 13.2+/-5.4, 25.3+/-6.1, 46.5+/-8.2, and 63.4+/-10.2 mmHg, respectively. The duration of tumescence ranged from 11.5-43.7 min. 7 The results show that berberine possesses a relaxant effect on rabbit corpus cavernosal tissues which is attributable to both endothelium-dependent and-independent properties. While the former component is apparently due to the release of NO from sinusoidal endothelium, the endothelium-independent mechanism involved in berberine relaxation is probably linked to ChTX- and 4-AP-sensitive K+ channel activation in the cavernosal vasculature.