Development and Therapeutic Applications of Nitric Oxide Releasing Materials to Treat Erectile Dysfunction

Figures & data

Figure 1.  Nitric oxide pathways involved in erectile physiology.

The initiation of penile erection is controlled by the parasympathetic and sympathetic branches of the autonomic nervous system. Nerve stimulation activates the release of NO from nNOS. This then initiates a cascade effect, activating NO production in endothelial cells through eNOS and iNOS. NO then activates guanylate cyclase, which induces corporal smooth muscle relaxation by increasing intracellular cGMP, which primarily through activation of potassium channels inhibits calcium entry into the cell thereby decreasing intracellular calcium concentrations. Intracellular calcium is the prime determinant of the activity of MLCK. With lower calcium levels in the cell, the predominant direction of myosin is toward dephosphorylation (mediated though MLCK), which leads to smooth muscle relaxation.

eNOS: Endothelial nitric oxide; iNOS: Inducible nitric oxide; MLCK: Myosin light chain kinase; NO: Nitric oxide; nNOS: Neuronal nitric oxide synthase; NOS: Nitric oxide synthase.

Figure 2.  The metabolism of nitric oxide generating substrates which have been investigated for their ability to treat erectile dysfunction.

NO: Nitric oxide; NOS: Nitric oxide synthase.

Figure 3.  Example of a continuous trace of intracorporal pressure (upper panel) and systemic blood pressure (lower panel) over the course of an experiment following administration of 200 μl NO-nanoparticles performed topically on the rat penis.

The time points of application of the NO-nanoparticles are shown by the arrows.

NO: Nitric oxide.

Reproduced with permission from [24] © Wiley (2010).

Han G , TarM, KuppamDSet al. Nanoparticles as a novel delivery vehicle for therapeutics targeting erectile dysfunction. J. Sex. Med.7(1 Pt 1), 224–233 (2010).

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