The relaxation of isolated rabbit corpus cavernosum by the herbal medicineCatuama (R) and its constituents

The effects of the Brazilian herbal medicine Catuama (R) and each of its pl ant constituents (Paullinia cupana, Trichilia catigua, Zingiber officinalis and Ptychopetalum olacoides) were investigated on rabbit corpus cavernosum (RbCC) using a bioassay cascade. Catuama (R) caused short-lived and dose-d ependent relaxations (11% +/- 7%, 26% +/- 5% and 82% +/- 9%, at doses of 1, 3 and 10 mg, respectively). Neither the nitric oxide synthesis inhibitor N -omega-nitro-L-arginine methyl ester (L-NAME; 10 muM) nor the soluble guany late cyclase inhibitor ODQ (10 muM) significantly affected the Catuama (R) -induced relaxations. Similarly, the selective ATP-dependent K+ channel (K- ATP) blocker glibenclamide (10 muM), the muscarinic receptor antagonist atr opine (1 muM) and the voltage-dependent Na+ channel blocker tetrodotoxin (1 muM) all failed to affect significantly the Catuama (R) -induced relaxatio ns. These results indicate that the relaxations induced by Catuama (R) invo lve neither nitric oxide release nor KATP channel activation. The extracts of P. cupana, Z. officinalis and P. olacoides caused short-lived and dose-d ependent RbCC relaxations, whereas T. catigua evoked long-lasting relaxatio ns which were occasionally preceded by a brief contractile effect. The extr act of A cupana was the most active in relaxing RbCC strips. The relaxation s induced by all extracts were not significantly affected by L-NAME (10 muM ). The infusion of ODQ (10 muM) had no significant effect on the P. cupana- and Z. officinalis-induced relaxations but reduced by > 50% (p < 0.05) tho se evoked by A olacoides and T. catigua. Incubations of RbCC with Catuama ( R) (10 mg/mL for 0.25 to 5 min) caused increases of cAMP levels (143% incre ase at 5 min of incubation). Incubations of RbCC with A cupana extract (1 m g/mL) increased the cAMP levels by 200% whereas higher doses (10 and 100 mg /mL) caused smaller increases in the nucleotide levels (150% and 89%, respe ctively). The extracts of Z. officinalis and P. olacoides (same doses) caus ed smaller increases of the cAMP levels compared with the A cupana extract, whereas T. catigua (1-100 mg) did not increase the levels of this nucleoti de above the basal values. Our results show that of the four extracts assay ed, P. cupana was the most effective, indicating that it is the main extrac t responsible for the relaxing effect of Catuama (R) on rabbit cavernosal t issue. Copyright (C) 2001 John Wiley & Sons, Ltd.