[Mechanisms of hypertension inducing erectile dysfunction via the cGMP/PKG signaling pathway: An investigation using transcriptomics and network pharmacology].

OBJECTIVE

To explore the mechanism of hypertension inducing erectile dysfunction (ED) using transcriptomics and network pharmacology.

METHODS

We randomly divided 12 male rats with spontaneous hypertension (SHT) into an L-arginine (LA) group (n = 6) and an SHT model control (MC) group (n = 6), took another 6 Wistar Kyoto male rats as normal controls (NC), and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physiological saline, once a day, all for 7 days. Then we observed the blood pressure and penile erection of the rats, and determined the expressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA, Western blot and RT-qPCR.

RESULTS

Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED. In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group (1.33 ± 0.52 vs 2.67 ± 0.51, P<0.05). The protein expressions of eNOS, PKG and sGC were markedly decreased in the model controls compared with those the normal controls (P<0.05), but remarkably upregulated in the LA group compared with those in the MC group (P<0.05).

CONCLUSION

Hypertension decreases the expressions of eNOS, NO, sGC, cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway, which consequently suppresses the relaxation of the penile vascular smooth muscle and reduces erectile function.