Combination Of Herba Epimedii And Semen Plentaginis Mediates Antihypertensive And Improves Erectile Function Effects By Upregulating The ACE2/angiotensin-(1-7)/Mas Receptor Axis In Spontaneously Hypertensive Rats

BackgroundThe angiotensin-converting enzyme 2–angiotensin-(1–7)–Mas receptor(ACE2/Ang-[1–7]/Mas receptor)axis is involved in the pathogenesis of essential hypertension and contribute to the pathogenesis of erectile dysfunction(ED)complicated by essential hypertension(EH).ObjectiveWe evaluated the effects of combination of Herba Epimedii and Semen Plentaginis(HESP)on blood pressure,aortic intima media thickness(IMT)and erectile function in spontaneously hypertensive rats(SHR)and elucidated the role of the ACE2/Ang-(1–7)/Mas receptor axis in the process.Methods:A total of 24 SHR were randomly assigned to the following three groups: SHR-control,low-dose HESP(12.5 g/kg),and high-dose HESP(25 g/kg).Eight Wistar-Kyoto(WKY)rats were selected as the normal control.HESP was administered by gavage for 4 weeks.Systolic blood pressure and diastolic blood pressure(SBP/DBP)were measured once per week in conscious rats using tailcuff plethysmograph.Erectile function was measured once-a-week using the Heaton test.ResultAfter 4 weeks of treatment,thoracic aortas,corpus cavernosum and plasma of each rat were harvested to measure IMT,erectile function,nitric oxide(NO),endothelial nitric oxide synthase(eNOS),and Ang-(1–7)levels,as well as ACE2,Mas receptor,and neuronal nitric oxide synthase(nNOS)protein expression.Four weeks of HESP treatment significantly decreased SBP,DBP and aortic IMT compared to the SHR-control group(p < 0.05 or p < 0.01).In addition,treatment with HESP significantly increased erectile function,plasma Ang-(1–7)levels and aortic Ang-(1–7),NO and eNOS levels.Moreover,HESP treatment significantly increased ACE2,Mas receptor,and nNOS protein expression.These beneficial effects were particularly pronounced in the high-dose HESP group.BP and IMT in the control group were significantly higher than the normal group of WKY rats(P < 0.05 or P < 0.01),and the erectile function was significantly weakened compared with the normal group WKY rats(P < 0.01).The concentration of Ang-(1–7),NO and eNOS in the aorta and the corpus cavernosum,ACE2,Mas receptor,and nNOS protein expression decreased significantly compared with normal group.ConclusionHESP attenuates SBP,DBP and aortic IMT,increases erectile function by upregulating the ACE2/Ang-(1-7)/Mas receptor axis and nNOS/eNOS pathways in SHR.Compared with WKY rats,SHR featured erectile dysfunction and ACE2-Ang(1-7)-Mas axis-eNOS/nNOS pathway down-regulating.