Copyright © 2006, European Society of Cardiology
Perivascular adipose tissue promotes vasoconstriction: the role of superoxide anion
aSmooth Muscle Research Program and Department of Anaesthesia, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5
bDepartment of Medicine, McMaster University, Hamilton, Ontario, Canada
* Corresponding author. Tel.: +1 905 521 2368x75433; fax: +1 905 523 1224. Email address: gaoyu{at}mcmaster.ca
Objectives Recent studies have demonstrated that perivascular adipose tissue (PVAT) releases vascular relaxation factor(s). In this study, we examined if PVAT releases other vasoactive factors in response to perivascular nerve activation by electrical field stimulation (EFS).
Methods and results In Wistar-Kyoto rats, rings of superior mesenteric artery (MA) with intact PVAT (PVAT (+)) showed a greater contractile response to EFS than rings with PVAT removed (PVAT (–)). Superoxide dismutase (SOD) reduced the contractile response to EFS more in PVAT (+) MA than in PVAT (–) MA. Inhibitors of NAD(P)H oxidase and cyclooxygenase exerted a greater inhibition on EFS-induced contraction in PVAT (+) MA than in PVAT (–) MA. Inhibitors of tyrosine kinase (tyrphostin A25) and MAPK/ERK (U 0126) attenuated EFS-induced contraction in PVAT (+) MA in a concentration-related manner, while inactive forms of these inhibitors (tyrphostin A1 and U 0124) did not inhibit the response. Exogenous superoxide augmented the contractile response to EFS and to phenylephrine in PVAT (–) MA, and this augmentation was blunted by inhibition of tyrosine kinase and MAPK/ERK. EFS increased superoxide generation in isolated PVAT and PVAT (+)/(–) MA, which was attenuated by NAD(P)H oxidase inhibition. RT-PCR showed the mRNA expression of p67phox subunit of NAD(P)H oxidase and immunohistochemical staining confirmed its localization in the adipocytes of PVAT.
Conclusion These results show that PVAT enhances the arterial contractile response to perivascular nerve stimulation through the production of superoxide mediated by NAD(P)H oxidase, and that this enhancement involves activation of tyrosine kinase and MAPK/ERK pathway.
KEYWORDS Adipose tissue; Contraction; MAPK; Mesenteric artery; Perivascular nerve stimulation; Superoxide anion
Time for primary review 28 days
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