Chemical renal denervation-induced upregulation of the ACE2/Ang (1-7)/Mas axis attenuates blood pressure elevation in spontaneously hypertensive rats

Clin Exp Hypertens. 2020 Oct 2;42(7):661-668. doi: 10.1080/10641963.2020.1772812. Epub 2020 Jun 1.

Abstract

Objective: Evidence has shown that the ACE2/Ang (1-7)/Mas axis plays an important role in the control of hypertension. Thus, we hypothesized that chemical renal denervation (RDN) could reduce blood pressure by regulating the ACE2/Ang (1-7)/Mas axis in spontaneously hypertensive rats.

Methods: Twelve rats were randomly divided into sham group and chemical RDN group. All the rats were sacrificed 4 weeks later. Plasma samples were collected to measure the renin-angiotensin system (RAS) activities and reactive oxygen species levels by radioimmunoassay, chromatometry and ELISA. Paraventricular nucleus (PVN) tissues were collected to examine the expression of the components of the ACE2/Ang (1-7)/Mas axis by western bolt and immunofluorescence.

Results: The systolic blood pressure (169.33 ± 7.50 vs 182.67 ± 7.00 mmHg, p < .05) and the diastolic blood pressure (97.50 ± 4.68 vs 109.33 ± 4.41 mmHg, p < .05) in the RDN group were obviously lower than the baseline levels, whereas the opposite results were observed in the sham group. The RDN group exhibited a significant reduction in the plasma ROS (91.59 ± 13.12 vs 72.34 ± 11.76 U/ml, p < .05) and NADPH oxidase (171.86 ± 1.14 vs 175.75 ± 1.74 nmol/ml, p < .001) compared with the sham group, while the plasma eNOS (3.47 ± 0.42 vs 2.49 ± 0.51 U/ml, p < .05) and NO (55.92 ± 8.10 vs 43.53 ± 4.58 μmol/L, p < .05) were increased. The expression of the components of the ACE2/Ang (1-7)/Mas axis was upregulated while the expression of the components of the ACE/Ang II/AT1 R axis was downregulated in the plasma and PVN in the RDN group.

Conclusion: Our findings suggested that the reduction in blood pressure was regulated by chemical RDN-induced upregulation of the components of the ACE2/Ang (1-7)/Mas axis.

Keywords: ACE2/Ang (1-7)/Mas; Renal denervation; hypertension.

MeSH terms

  • Angiotensin I / metabolism*
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Blood Pressure*
  • Hypertension / physiopathology
  • Male
  • NADPH Oxidases / blood
  • Nitric Oxide / blood
  • Nitric Oxide Synthase Type III / blood
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Peptide Fragments / metabolism*
  • Peptidyl-Dipeptidase A / metabolism*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / metabolism*
  • Random Allocation
  • Rats
  • Rats, Inbred SHR
  • Reactive Oxygen Species / blood
  • Receptors, G-Protein-Coupled / metabolism*
  • Renal Artery / innervation
  • Renin-Angiotensin System
  • Sympathectomy, Chemical*
  • Up-Regulation

Substances

  • Peptide Fragments
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Reactive Oxygen Species
  • Receptors, G-Protein-Coupled
  • Nitric Oxide
  • Angiotensin I
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • NADPH Oxidases
  • Peptidyl-Dipeptidase A
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)