Oral phosphodiesterase-5 inhibitors: effect of heme oxygenase inhibition on cGMP signalling in rat cavernous tissue

Authors: Abdel Aziz, M. T.1; Mostafa, T.2; Atta, H.1; Rashed, L.1; Marzouk, S. A.1; Obaia, E. M.1; Sabry, D.1; Hassouna, A. A.1; El-Shehaby, A. M.1; Abdel Aziz, A.T.1

Source: Andrologia, Volume 39, Number 2, April 2007 , pp. 66-70(5)

Publisher: Blackwell Publishing

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Abstract:

Summary

This work postulated that heme oxygenase (HO) is partly responsible for controlling phosphodiesterase-5 inhibitor actions by modulating cyclic guanosine monophosphate (cGMP) cavernous tissue levels. Five hundred and four male Sprague-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 protoporphyrin. 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 tissues 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; PDE inhibitors; sildenafil; tadalafil; vardenafil

Document Type: Research article

DOI: 10.1111/j.1439-0272.2007.00765.x

Affiliations: 1: Molecular Biology Unit, Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt; 2: Department of Andrology & Sexology, Faculty of Medicine, Cairo University, Cairo, Egypt

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