Penile erectile activity of dinitrosyl iron complexes with thiol-containing ligands

It has been established that intracavernous injections of water-soluble dinitrosyl iron complexes (DNIC) with glutathione or cysteine (0.4-6.0 mu moles/kg) to male rats induce short-term (2-3 min) penile erection along with a short-term drop of arterial pressure and appearance of protein-bound DNIC in cavernous tissue and circulating blood. The duration of erection and the hypotensive activity of DNIC increase dramatically after simultaneous intracavernous injection of DNIC and the phosphodiesterase-5 inhibitor papaverine. Surgical denervation of cavernous bodies does not influence the erectile activity of DNIC. No penile erection takes place after intravenous (instead of intracavernous) injection of the same dose of DNIC; in this case, protein-bound DNIC are detected only in the blood. These findings suggest that water-soluble DNIC with thiol-containing ligands (cysteine or glutathione) can be used as a basis in the design of a novel class of drugs for treating erectile dysfunctions. (C) 2011 Elsevier Inc. All rights reserved.