188 The Influence of Maternal Obesity on Perivascular Adipose Tissue Function in Offspring. (6th June 2015)

• Record Type: Journal Article
• Authors: Zaborska, Karolina; Edwards, Gillian; Austin, Clare; Wareing, Mark
• Is Part Of: Heart. Volume 101(2015)Supplement 4
• Page Start: A105
• Page End: A105
• Publication Date: 2015-06-06
• Subjects: PVAT -- Maternal obesity -- AMPK; Heart -- Diseases -- Treatment -- Periodicals; Cardiology -- Periodicals; 616.12
• DOI: 10.1136/heartjnl-2015-308066.188
• Languages: English
• ISSNs: 1355-6037

Abstract

Abstract : Objective: Maternal obesity pre-programmes offspring to develop obesity, glucose intolerance and associated cardiovascular disease later in life although the underlying mechanism is currently unknown. This study investigated the effect of a maternal high fat diet on perivascular adipose tissue (PVAT) regulation of resistance artery tone. Design and method: 8 week old female SD rats were fed a 10% fat diet (controls) or 45% fat obesogenic diet (HFD) for 12 weeks before mating then continued on their respective diets during pregnancy and lactation. PVAT-intact or -denuded mesenteric arteries from dams and pups (250–300 µm internal diameter) were mounted on a wire myograph. Cumulative concentration-response curves were constructed to thromboxane A2 receptor agonist U46619 (10 nM–3 µM) ± 10 µM A769662, an activator of AMP-activated kinase (AMPK), and/or 100 µM L-NMMA, a nitric oxide synthase (NOS) inhibitor. Results: Body weight (BW) and systolic (SBP) and diastolic (DBP) blood pressure were significantly increased in HFD dams (BW: p < 0.05, SBP: p < 0.001, DBP: p < 0.01) and their offspring at 24 weeks (BW <0.0001, SBP: p < 0.0001, DBP: p < 0.0001) compared to controls but no differences were observed in offspring at 12 weeks. PVAT exerted an anti-contractile effect in artery segments from control dams and their offspring at 12 and 24 weeks (p < 0.01, p < 0.001, p < 0.05), an effect which was lost in both dams fed HFD and their offspring. AMPK activation decreased contractility of both PVAT-denuded and intact control vessels in the presence and absence of a NOS inhibitor in control dams (p < 0.0001) and their offspring (p < 0.0001); this effect was decreased in PVAT-intact vessels of HFD dams and their offspring. Conclusions: In summary, the attenuated anti-contractile effects of PVAT in HFD dams and their offspring may be modulated by AMPK; however it is not totally dependent on nitric oxide release.