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

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Abstract
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 microM)-dependent relaxation in phenylephrine (PE)-precontracted corpus cavernosum. 3. Tetrodotoxin (0.1 and 1 microM) treatment had no significant effect on the berberine-induced relaxation. Phentolamine (1 and 10 microM), propranolol (1 and 3 microM) and atropine (1 and 3 microM) 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-NG-nitro arginine methyl ester (0.1 and 0.3 mM), but not indomethacin (30 microM). 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.