Mechanisms of hypertension inducing erectile dysfunction via the cGMP/PKG signaling pathway:An investigation using transcriptomics and network pharmacology
10.13263/j.cnki.nja.2024.09.001
- VernacularTitle:转录组学联合网络药理学探究高血压通过cGMP/PKG信号通路诱导勃起功能障碍的机制
- Author:
Jun-Long FENG
1
;
Hai-Song LI
;
Song SUN
;
Bin WANG
;
Hua-Nan ZHANG
;
Zi-Xiang GAO
;
Peng-Ming MAO
;
Long-Ji SUN
;
Nian-Wen HUANG
;
Ji-Sheng WANG
Author Information
1. 北京中医药大学东直门医院男科,北京 100700
- Keywords:
transcriptomics;
network pharmacology;
hypertension;
erectile dysfunction;
cGMP/PKG signaling pathway
- From:
National Journal of Andrology
2024;30(9):771-781
- CountryChina
- Language:Chinese
-
Abstract:
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 physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions 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 de-creased in the model controls compared with those the normal controls(P＜0.05),but remarkably upregulated in the LA group com-pared 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 relaxa-tion of the penile vascular smooth muscle and reduces erectile function.
