Oral phosphodiesterase-5 inhibitors: Effect of heme oxygenase inhibition on cGMP signaling in rat cavernous tissue.

Citation:
Aziz, A. M. T., T. Moustafa, H. Atta, L. Rashed, S. A. Marzouk, E. M. Obaia, D. Sabry, A. A. Hassouna, E. A. M. Shehaby, and A. A. T. Aziz, "Oral phosphodiesterase-5 inhibitors: Effect of heme oxygenase inhibition on cGMP signaling in rat cavernous tissue.", Andrologia, vol. 39, issue 2, pp. 66-70, 2007.

Abstract:

Abstract
Summary. This Work postulated that heme oxygenase (HO) is partly responsible for con-trolling phosphodiesterase-5 inhibitor actions by modulating cyclic guanosine monophosphate (cGMP) cavernous tissue levels. Five hundred and four maleSprague-Dawley rats, divided into five groups, were investigated.Group 1 (n = 72) included controls, Group 2 (n = 72) received sildenafil citrate (ViagraR) Orally, Group 3 (n = 72) received vardenafil hydrochloride (LevitraR), group 4 (n = 72) received tadalafil (cialisR). Group 5 (n = 216), subdivided into three subgroups (A, B and C, 72 each), received the same dose of each drug with the HO inhibitor, Zn proptoporphyrin. Eight rats from each group / subgroup were killed at 0.5, 1, 2, 3, 4, 6, 18, 24 and 36 h when cGMP levels in the cavernous tissue were estimated. Cavernous tissue cGMP levels increased significantly in sildenafil, vardenafil and tadalafil-treated rats compared to the controls with significant decreases after HO inhibition. It is concluded that the effects of these PDE-5 inhibitors in rat cavernous tissue are partly mediated through HO activity via the cGMP signalling pathway.
Keywords. cGMP—erectile dysfunction—heme oxygenase—PDF inhibitors—sildenafil— tadalafil —vardenafil.

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