Stimulation of P2y purinoceptors induces, via nitric oxide production, endothelium-dependent relaxation of human isolated corpus cavernosum

Purpose: Endothelial P2y purinoceptor stimulation is known to induce vasodi latation mediated by NO release from endothelial cells. We examined the eff ect of a potent P2y agonist, adenosine5'-O-(2-thiodiphosphate) (ADP beta S) , on human corporal cavernosal strips and its dependence on a functional en dothelial lining. Materials and Methods: The preparations mounted in isometric conditions wer e precontracted by noradrenaline (NA) at a concentration of 0.1 mu M. Incre asing concentrations of ADP beta S from 1 mu M to 100 mu M were added in th e presence and absence of a functional endothelium or in the presence and a bsence of an NO synthase inhibitor and a selective P2y antagonist. Acetylch oline (Ach)-induced relaxation was used in each experiment for control. Results: In human precontracted corporal cavernosal strips with a functiona l endothelium (relaxed by acetylcholine) ADP beta S induces a dose-dependen t relaxation with maximal relaxation of 45.5 +/- 5.0% and an EC50 of 11.7 m u M. The relaxant effect of ADP beta S was reduced by 77.1 +/- 7.0% by reac tive blue 2 (20 mu M)(a P2y antagonist). L-NAME (L-Nitro Arginin Methyl Est er), an NO synthase inhibitor (100 mu M), reduced Ach- and ADP beta S- indu ced relaxations by 86.59 +/- 3.24% and 86.83 +/- 0.5% respectively. Ach- an d ADP beta S- induced relaxations were significantly inhibited after dislod ging of the endothelial. Lining of the corporal cavernosal strips, 90.11 +/ - 6.2% and 87.1 +/- 5% respectively. Conclusions: Human corporal cavernosal strips can be relaxed by stimulation of P2y purinoceptors via NO release. This relaxation is an endothelium-dep endent mechanism. Purines may be implicated in physiological erection in ma n.