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

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:

• Renal denervation
• hypertension
• ACE2/Ang (1-7)/Mas

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was partly supported by the National Natural Science Foundation of China (81370361), Science and Technology Commission of Shanghai Municipality (12140902800), Research Fund for the Scientific and Technical Project of Shanghai Chest Hospital (2014YZDH20300).