Key result
Acute exposure of murine perivascular adipose tissue to peroxynitrite significantly enhanced its anticontractile effect, increasing maximal vessel relaxation from 43.73% to 64.45%.
Why the study?
PVAT function changes in cardiovascular diseases like diabetes and hypertension, and the effect of peroxynitrite on PVAT function is unknown.
Does acute exogenous peroxynitrite exposure improve vascular relaxation and adiponectin production in murine perivascular adipose tissue?
Does acute exogenous peroxynitrite exposure improve vascular relaxation and adiponectin production in murine perivascular adipose tissue?
Acute exposure to peroxynitrite paradoxically enhances the anticontractile function of perivascular adipose tissue by upregulating adiponectin production, suggesting a short-term compensatory defense mechanism against oxidative stress.
May enhance PVAT anticontractile function in oxidative stress; hypothesis-generating in murine models only.
Perivascular adipose tissue (PVAT) surrounds the exterior of blood vessels and releases numerous substances such as adiponectin which positively modulate blood vessel tone. In some cardiovascular diseases such as diabetes and high blood pressure, the function of PVAT changes and we speculate that oxidant stress may play a role in this change. PVAT has the ability to generate both superoxide and nitric oxide and these can combine rapidly under physiological conditions to form peroxynitrite (ONOO-). In disease states, the production of ONOO- may be increased and so its effect on the function of PVAT is of great interest. Consequently, we studied the effects of acute addition of the oxidant species ONOO- on vascular tone and production of adiponectin by mouse thoracic aortic PVAT. Murine PVAT was immunostained for nitrotyrosine, indicating that ONOO- is formed in the PVAT. Exogenous ONOO- significantly increased the anticontractile effect of PVAT via increased adiponectin content but had no effect on eNOS expression or phosphorylation. These results suggest that generation of ONOO- within PVAT may be an important regulatory mechanism which influences the activity of PVAT. The effect of chronic exposure to raised levels of ONOO- on PVAT function remains to be determined.
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Ugusman et al. (2019) studied Healthy and AMPK α1 knockout mice (n=34). Peroxynitrite (ONOO-) vs. Untreated perivascular adipose tissue (PVAT) was evaluated on Maximal relaxation to cromakalim in aortic rings (p=<0.001). Acute exposure of murine perivascular adipose tissue to peroxynitrite significantly enhanced its anticontractile effect, increasing maximal vessel relaxation from 43.73% to 64.45%.
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