Abstract

Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders. The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2-/y) animals. Experiments were performed in 20–22 week-old C57BL/6 and ACE2-/y male mice. Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2-/y mice. Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in •NO concentrations were observed in aortas of ACE2-/y mice in comparison to controls. Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced •NO availability in ACE2-deficient animals. Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2-/y mice, indicating impaired antioxidant capacity. Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress. In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis. Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance.

Highlights

  • The prevalence of cardiovascular diseases is one of the major public health problems [1]

  • To evaluate if angiotensin-converting enzyme 2 (ACE2)-deficiency affects vascular function, we investigated the vascular reactivity in vivo in conscious ACE2-/y mice by bolus intra-aortic administration of the endothelium-dependent vasodilator acetylcholine (ACh)

  • We took advantage of a mouse model with genetic deletion of ACE2 to address the role of this enzyme in the regulation of the balance between O2- and released NO within the endothelial environment which is pivotal in the maintenance of vascular homeostasis [18,30]

Read more

Summary

Introduction

The prevalence of cardiovascular diseases is one of the major public health problems [1]. The interplay in the triad renin-angiotensin system (RAS), endothelial function (EF), and oxidative stress plays a key role in cardiovascular and metabolic homeostasis and, in the pathogenesis of these diseases [2,3].

Objectives
Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call