Perivascular adipose tissue promotes vasoconstriction: the role of superoxide anion.
نویسندگان
چکیده
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 p(67phox) 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.
منابع مشابه
Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction in a rodent model of metabolic syndrome.
The metabolic syndrome represents a constellation of cardiovascular risk factors that promote the development of cardiovascular disease. Oxidative stress is a mediator of endothelial dysfunction and vascular remodeling. We investigated vascular dysfunction in the metabolic syndrome and the oxidant mechanisms involved. New Zealand obese (NZO) mice with metabolic syndrome and New Zealand black co...
متن کاملRegulation of Vascular Smooth Muscle Tone by Adipose-Derived Contracting Factor
Obesity and arterial hypertension, important risk factors for atherosclerosis and coronary artery disease, are characterized by an increase in vascular tone. While obesity is known to augment vasoconstrictor prostanoid activity in endothelial cells, less is known about factors released from fat tissue surrounding arteries (perivascular adipose). Using lean controls and mice with either monogeni...
متن کاملThe Interaction between Trolox and 4,4’-diisothiocyanatostilbene-2,2’-disulfonic Acid on Hypoxic Pulmonary Vasoconstriction in the Isolated Rabbit Lung
Background: The mechanism of hypoxic pulmonary vasoconstriction (HPV) is still debatable. It has been proposed that reactive oxygen species (ROS) might be involved in HPV. However, there is no special transporter for superoxide anion in the cell membrane and it may release from the cells via anion exchanger. Therefore, the aim of this study was to investigate the interaction of ROS and anion ex...
متن کاملThe Role of Inflammation and Changes of Adipose Tissue-Resident Immune Cells in Increasing the Risk of Cancer: A Narrative Review
The incidence of obesity, as a major health problem, has increased significantly over the past decades. This condition is associated with an increased risk of cancers, type 2 diabetes, and cardiovascular diseases. The current study aimed to investigate the effects of inflammation and changes of adipose tissue-resident immune cells on increasing the risk of cancer in obese individuals. In obesit...
متن کاملTumour necrosis factor-alpha participates on the endothelin-1/nitric oxide imbalance in small arteries from obese patients: role of perivascular adipose tissue.
AIMS We assessed the impact of vascular and perivascular tumour necrosis factor-alpha (TNF-α) on the endothelin (ET)-1/nitric oxide (NO) system and the molecular pathways involved in small arteries from visceral fat of obese patients (Obese) and Controls. METHODS AND RESULTS Isolated small arteries from 16 Obese and 14 Controls were evaluated on a pressurized micromyograph. Endogenous ET-1 ac...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cardiovascular research
دوره 71 2 شماره
صفحات -
تاریخ انتشار 2006