Upregulation of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis by a combination of Yinyanghuo (Herba Epimedii Brevicornus) and Cheqianzi (Semen Plantaginis) improves erectile function in spontaneously hypertensive rats

J Tradit Chin Med. 2020 Oct;40(5):836-844. doi: 10.19852/j.cnki.jtcm.2020.05.014.

Abstract

Objective: To evaluate the effects of a combination of Yinyanghuo (Herba Epimedii Brevicornus) (HEB) and Cheqianzi (Semen Plantaginis) (SP) on erectile dysfunction caused by essential hypertension in spontaneously hypertensive rats (SHRs), and to elucidate the role of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor (ACE2/Ang [1-7]/Mas receptor) axis in this process.

Methods: A total of 24 SHRs were randomly assigned to three groups: SHR-control, low-dose (12.5 g/kg) and high-dose (25 g/kg) HEB+SP (HEBSP). Eight Wistar-Kyoto rats were used as normal controls. HEBSP was administered by oral gavage for 28 d. Erectile function was measured once a week using the Heaton test. After 4 weeks of treatment, the corpus cavernosum was harvested from each rat to measure nitric oxide (NO), nitric oxide synthase (eNOS) and Ang (1-7) levels, as well as ACE2, Mas receptor and neuronal nitric oxide synthase (nNOS) protein expression.

Results: After 4 weeks of treatment, HEBSP significantly increased erectile function in the treated group compared with SHR-control group (P < 0.01). Additionally, HEBSP treatment significantly increased cavernosal levels of Ang (1-7), eNOS and NO. Moreover, HEBSP significantly elevated the expression levels of ACE2, Mas receptor and nNOS. These beneficial effects were elevated in the high-dose HEBSP group.

Conclusion: HEBSP improved erectile function in SHRs by upregulating the ACE2/Ang (1-7)/Mas receptor axis, eNOS and nNOS pathways.

Keywords: Angiotensin; Cheqianzi (Semen Plantaginis); Corpus cavernosum; Nitric oxide synthase; Peptidyl-Dipeptidase A; Rats, Inbred SHR; Yinyanghuo (Herba Epimedii Brevicornus).

MeSH terms

  • Angiotensin I / genetics
  • Angiotensin I / metabolism*
  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Animals
  • Drug Therapy, Combination
  • Drugs, Chinese Herbal / administration & dosage*
  • Erectile Dysfunction / drug therapy*
  • Erectile Dysfunction / genetics
  • Erectile Dysfunction / metabolism*
  • Erectile Dysfunction / physiopathology
  • Humans
  • Male
  • Nitric Oxide Synthase Type I / genetics
  • Nitric Oxide Synthase Type I / metabolism
  • Penile Erection / drug effects
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Up-Regulation / drug effects

Substances

  • Drugs, Chinese Herbal
  • Peptide Fragments
  • Angiotensin I
  • Nitric Oxide Synthase Type I
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)