Effects of arginase inhibitors on the contractile and relaxant responses of isolated human penile erectile tissue

Abstract

An impairment in the local availability of nitric oxide (NO) may impair male erectile function. The activity of l-arginine-degrading arginase enzymes may attenuate the relaxation of cavernous smooth muscle by reducing local NO production. Arginase enzymes compete with the nitric oxide synthases for the common substrate, the amino acid l-arginine. Very little data are available regarding the significance of arginase enzymes in the control of human penile erectile tissue. The aim of the present study was to elucidate the effects of drugs known to inhibit arginase activity on the relaxation of isolated human corpus cavernosum (HCC) and the production of cyclic GMP. Using the organ bath technique, the effects of the arginase inhibitors DFMO, H-Orn-OH·HCl, H-lle-OH and nor-NOHA (10 nM–10 μM) on the tension induced by NE (1 μM) and the relaxation induced by electrical field stimulation (EFS) of HCC were investigated. HCC strips were also exposed to increasing concentrations of the compounds, and the production of cGMP was determined by means of a radioimmunoassay. Only marginal effects of the arginase inhibitors were registered on the tension induced by NE and the relaxation exerted by EFS. Mean reversion of tension ranged from 18 to 8%. Only DFMO and nor-NOHA amplified the EFS-induced relaxation by 11 and 29%, respectively. These effects were not paralleled by an increase in tissue levels of cGMP. Arginase inhibitors appeared to be ineffective in reversing the adrenergic tension and increasing the electrically induced relaxation of isolated HCC.