Effect of the plant-extract osthole on the relaxation of rabbit corpus cavernosum tissue in vitro.
OBJECTIVE
We investigated the cavernosal relaxant effect of osthole, a coumarin isolated from Cnidium monnier (L.) Cusson which has been long used in China as a herbal medicine to improve male sexual dysfunction.


METHODS
Strips of rabbit corpus cavernosum were precontracted with phenylephrine. Corporal relaxation evoked by osthole was then determined in the absence and presence of nitric oxide synthase inhibitor (L-NAME), soluble guanylate cyclase inhibitor (ODQ), cyclooxygenase inhibitor (indomethacin), tetradotoxin, and after endothelium deprivation.


RESULTS
Corpus cavernosal strips showed relaxation in response to osthole (0.1 approximately 30 microM) in a dose-dependent manner. These effects were reduced partially but significantly by pretreatment with L-NAME, ODQ and by endothelial disruption. However, they were not affected by indomethacin and tetradotoxin treatment. Osthole pretreatment (from 1 to 30 microM) enhanced the sodium nitroprusside (0.3 microM)-induced relaxation of corpus cavernosum in a dose-dependent manner to a maximum of 3 times the pretreatment level at 30 microM osthole. However, this effect was abolished in the presence of zaprinast. Additionally, a higher concentration of osthole (30 microM) also enhanced forskolin-induced relaxation.


CONCLUSIONS
The data suggested that osthole possesses a relaxant effect on rabbit corpus cavernosal tissues which is attributable to the release of NO from sinusoidal endothelium and to the potentiation of the cGMP and/or cAMP signal mediating relaxation of cavernosal smooth muscle by inhibiting phosphodiesterase.
Chen
J
J
Institute of Clinical Medicine, National Yang-Ming University, and National Research Institute of Chinese Medicine, Taipei, Taiwan, Republic of China.
Chiou
W F
WF
Chen
C C
CC
Chen
C F
CF
D000818:Animals; D003374:Coumarins / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010946:Plants, Medicinal; D011817:Rabbits
D003374:Coumarins; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D006162:Guanylate Cyclase; D019331:NG-Nitroarginine Methyl Ester; C046627:osthol; D007213:Indomethacin