Alteration of Redox Homeostasis and Protein Expression of Constitutive Nitric Oxide Synthases Contributes to Erectile Dysfunction of Heart Failure Rats

Abstract

The association of REDOX homeostasis (RH) and NO/cGMP signaling to development of chronic heart failure (CHF) has been investigated, but, alterations in these mechanism in the erectile dysfunction (ED) present in CHF are not well known. This study examined whether ED in rats submitted to arteriovenous fistula (volume overload) is mediated by changes in RH and/or NO/cGMP signaling. After 4 wks, intracavernosal pressure (ICP) was used to evaluate the erectile function (in vivo). Nitrergic and neurogenic responses induced by electrical‐field stimulation were obtained of corpus cavernosum rats (CCR; in vitro). Protein expression of endothelial‐ and neuronal‐nitric oxide synthases (eNOS, nNOS) were evaluated in CCR, as well as, plasmatic activity of superoxide dismutase (SOD) and T‐BARS. CHF rats (CHFR) showed the reduction of ICP in all frequency (P<0.01) compared to sham rats (SR). Nitrergic relaxation in CCR of CHFR was decreased at higher frequencies (16‐32 Hz; P<0.05), but, neurogenic contraction was increased at 32 Hz (P<0.05), compared to SR. Protein expression of eNOS and nNOS in the CCR of CHFR where reduced in 37% and 44%, respectively (P<0.05). CHFR showed a decreased of plasmatic activity SOD and an increase of T‐BARS (P<0.05). In conclusion, CHFR exhibit a reduction of eNOS and nNOS expression resulting in an impaired nitrergic response and increased the neurogenic response contributing to reduction of ICP, as well as, promote alteration in the RH, thus, these elements may contribute to development of ED in the CHF. Financial Support: FAPESP/CNPq.