Four-week oral guanosine treatment improves prostate and corpus cavernosum relaxation in obese mice

Guanosine is a guanine-derived nucleoside involved in the regulation of several physiological process. Experimental evidence indicates that guanosine promotes endothelium-independent vascular relaxation, enhances tadalafil-induced responses in the corpus cavernosum via cGMP signalling. Obesity, a major risk factor for lower urinary tract disorders and erectile dysfunction, is associated with impaired NO–sGC–cGMP signalling and functional alterations in urogenital tissues. Therefore, this study aimed to investigate whether chronic guanosine treatment modulates contractile dysfunction associated with obesity in the prostate and corpus cavernosum. C57BL/6 mice were divided into three groups: (i) lean, (ii) obese, and (iii) obese treated with guanosine (60 mg/kg, 4 weeks). Prostate and corpus cavernosum were isolated for functional assays. Electrical field stimulation (EFS) and concentration–response curves (CRC) were performed in the prostate using phenylephrine in the presence or absence of ODQ and ZM241385/MRS1754, as well as CRCs to sodium nitroprusside and isoproterenol. In corpus cavernosum, responses to EFS and CRCs to acetylcholine, sodium nitroprusside, isoproterenol, tadalafil, and adenosine were evaluated. Intracellular levels of cAMP and cGMP were quantified by mass spectrometry. Intracelullar levels of cAMP were similar among groups. However, cGMP level were reduced in obese mice compared to lean group and guanosine treatment restored these levels. Guanosine reduced prostate hypercontractility and restored relaxation in obese mice. Inhibition of cGMP synthesis or blockade of cAMP pathways reversed the anticontractile effects induced by guanosine in the prostate. Guanosine increased intracellular cAMP, but not cGMP, levels in prostate tissue from obese mice. In corpus cavernosum, obesity reduced nitrergic relaxation and impaired response to SNP and Tadalafil. Guanosine treatment restored these responses and increased the potency of ACh. Adenosine induced relaxation was reduced in obese compared to lean group, and guanosine treatment improved its potency when compared to obese group. Four-week guanosine treatment ameliorated prostate hypercontractility and erectile dysfunction in obese mice.