169 COMP-4 Reduces Oxidative Stress Markers in the Rat Corpora Cavernosa and Media of the Penile Dorsal Artery

Abstract

In age related erectile dysfunction, there is a progressive aging dependent reduction in the corporal smooth muscle cells (CSMCs) with replacement by collagen. To combat these histological alterations, the aging CSMCs begin to produce nitric oxide (NO) via upregulation of the normally quiescent inducible nitric oxide synthase (iNOS) enzyme. In a recent study, it was shown that COMP-4, a compound composed of ginger, muira puama, Paulina cupana, and L-citrulline, stimulated production of iNOS in vitro while treatment of middle aged rats for two months with oral COMP-4 resulted in an increase in the CSMC content with a resultant improvement in erectile function. In this study, we investigate whether activation of the iNOS-NO-cGMP pathway by COMP-4 can reduce oxidative stress in both the CSMC and the media of the extra-corporal penile dorsal artery (PDA). Ten-month old Sprague Dawley rats were treated daily for two months with either vehicle (n=6) or COMP-4 (n=6) prior to euthanization. Rat penises were excised and then processed for immunohistochemical staining of both the cavernosa and PDA. Apoptosis was determined by TUNEL assay and cell proliferation by PCNA staining. Markers of oxidative stress were determined by nitrotyrosine (NT) and myeloperoxidase (MPO) while anti-oxidative activity was determined with heme oxygenase 1 (HO-1) expression. Cellular oxidative stress within the cavernosa was measured using the redox glutathione ratio (GSH/GSSG) from CSMC culture treated with or without COMP-4.