M Shalev1, F Staerman, H Allain, B Lobel, B Saïag. 1. Unité Biologie et Physiologie de la paroi vasculaire, Laboratoire de Physiologie, Faculté de Pharmacie, Rennes, France.
Abstract
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, adenosine-5'-O-(2-thiodiphosphate) (ADPbetaS), 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 microM. Increasing concentrations of ADPbetaS from 1 microM to 100 microM 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) ADPbetaS induces a dose-dependent relaxation with maximal relaxation of 45.5+/-5.0% and an EC50 of 11.7 microM. The relaxant effect of ADPbetaS was reduced by 77.1+/-7.0% by reactive blue 2 (20 microM)(a P2y antagonist). L-NAME (L-Nitro Arginin Methyl Ester), an NO synthase inhibitor (100 microM), reduced Ach- and ADPbetaS- induced relaxations by 86.59+/-3.24% and 86.83+/-0.5% respectively. Ach- and ADPbetaS- 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.
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, adenosine-5'-O-(2-thiodiphosphate) (ADPbetaS), 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 microM. Increasing concentrations of ADPbetaS from 1 microM to 100 microM 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) ADPbetaS induces a dose-dependent relaxation with maximal relaxation of 45.5+/-5.0% and an EC50 of 11.7 microM. The relaxant effect of ADPbetaS was reduced by 77.1+/-7.0% by reactive blue 2 (20 microM)(a P2y antagonist). L-NAME (L-Nitro Arginin Methyl Ester), an NO synthase inhibitor (100 microM), reduced Ach- and ADPbetaS- induced relaxations by 86.59+/-3.24% and 86.83+/-0.5% respectively. Ach- and ADPbetaS- 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.
Authors: Tiejuan Mi; Shahrzad Abbasi; Hong Zhang; Karen Uray; Janci L Chunn; Ling Wei Xia; Jose G Molina; Norman W Weisbrodt; Rodney E Kellems; Michael R Blackburn; Yang Xia Journal: J Clin Invest Date: 2008-04 Impact factor: 14.808