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 vasodilatation mediated by NO release from endothelial cells. We examined the effect of a potent P2y agonist, adenosine5'-O-(2-thiodiphosphate) (ADP beta S), on human corporal cavernosal strips and its dependence on a functional endothelial lining. Materials and Methods: The preparations mounted in isometric conditions were precontracted by noradrenaline (NA) at a concentration of 0.1 mu M. Increasing concentrations of ADP beta S from 1 mu M to 100 mu M were added in the presence and absence of a functional endothelium or in the presence and absence of an NO synthase inhibitor and a selective P2y antagonist. Acetylcholine (Ach)-induced relaxation was used in each experiment for control. Results: In human precontracted corporal cavernosal strips with a functional endothelium (relaxed by acetylcholine) ADP beta S induces a dose-dependent relaxation with maximal relaxation of 45.5 +/- 5.0% and an EC50 of 11.7 mu M. The relaxant effect of ADP beta S was reduced by 77.1 +/- 7.0% by reactive blue 2 (20 mu M)(a P2y antagonist). L-NAME (L-Nitro Arginin Methyl Ester), an NO synthase inhibitor (100 mu M), reduced Ach- and ADP beta S- induced relaxations by 86.59 +/- 3.24% and 86.83 +/- 0.5% respectively. Ach- and ADP beta S- induced relaxations were significantly inhibited after dislodging 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-dependent mechanism. Purines may be implicated in physiological erection in man.