The Relaxation Induced by Uroguanylin and the Expression of Natriuretic Peptide Receptors in Human Corpora Cavernosa

ABSTRACT Introduction Receptors for natriuretic peptides have been demonstrated as potential targets for the treatment of male erectile dysfunction. Aim This study investigates the relaxant effects of the atrial natriuretic peptide (ANP) and uroguanylin (UGN), and expression of natriuretic peptide receptors on strips of human corpora cavernosa (HCC). Main Outcome Measures Quantitative analysis of natriuretic receptor expression and relaxation of precontracted strips were used to assess the membrane-bound guanylate cyclase–cyclic guanosine monophosphate (cGMP) pathway in HCC strips. Methods HCC was obtained from a cadaver donor at the time of collection of organs for transplantation (14–47 years) and strips were mounted in organ baths for isometric studies. Results ANP and UGN both induced concentration-dependent relaxation on HCC strips with a maximal response attained at 300 nM, corresponding to 45.4 ± 4.0% and 49 ± 4.8%, respectively. The relaxation is not affected by 30 µM 1H-[1,2,4]oxaolodiazolo[4,3-a]quinoxalin-1-one (ODQ) (a soluble guanylate cyclase inhibitor), but it is significantly blocked by 10 µM isatin, a nonspecific particulate guanylate cyclase (pGC) inhibitor. UGN was unable to potentiate electrical field stimulation (EFS) or acetylcholine-induced relaxations. The potential role of pGC activation and cGMP generation in this effect is reinforced by the potentiation of this effect by phosphodiesterase-5 inhibitor vardenafil (55.0 ± 7.5-UGN vs. 98.6 ± 1.4%-UGN + vardenafil; P Conclusions UGN relaxes HCC strips by a guanylate cyclase and K ca -channel-dependent mechanism. These findings obtained in HCC reveal that the natriuretic peptide receptors are potential targets for the development of new drugs for the treatment of erectile dysfunction. Sousa CM, Havt A, Santos CF, Arnaud-Batista FJ, Cunha KMA, Cerqueira JBG, Fonteles MC, and Nascimento NRF. The relaxation induced by uroguanylin and the expression of natriuretic peptide receptors in human corpora cavernosa.