Introduction: Aging is widely considered the biggest independent risk factor for cardiovascular disease, the leading cause of death worldwide. Advanced age is associated with endothelial dysfunction, hypertension and increased risk of stroke and myocardial infarction; the mechanisms behind these increased risks are little understood. It has long been known that there is an age-related endothelial dysfunction, due to decreased bioavailability of the endogenous vasodilator nitric oxide (NO), synthesised in the vascular endothelium (Barton et al., 1997). Vascular reactivity is further regulated via the perivascular adipose tissue (PVAT), which has a net anti-contractile effect (Greenstein et al., 2009). PVAT is also known to be a source of NO (Gil-Ortega et al., 2010), in addition to secreting locally acting factors that augment endothelial NO production (Gao et al., 2007). Hypothesis: PVAT dysfunction may occur with aging, and is due at least in part to reduced bioavailability of NO. Methods and Results: Third order mesenteric arteries were taken from male Wistar rats aged 3 months old (m.o.), 12 m.o., 18 m.o. and 24 m.o. and contractility to increasing concentrations of the thromboxane A2 receptor agonist U46619 (10nM-3µM) assessed via wire-myography in the presence and absence of PVAT and the NO-synthase inhibitor Nω-nitro-L-arginine (L-NNA) (50µM). Results were analysed via two-way ANOVA (Bonferroni post-hoc). PVAT was anti-contractile in 3 m.o. rat arteries (-PVAT max change in tension to U46619 (mN/mm) +1.2±0.52 (n=6), +PVAT +0.55±0.07 (n=3)) and 12 m.o. rat arteries (-PVAT +0.61±0.06 (n=5), +PVAT +0.44±0.13 (n=5), p=0.0280) but that this effect had been lost by 18 months (-PVAT +0.99.±0.11 (n=7), +PVAT 0.96±0.18 (n=5)), and remained absent at 24 m.o. (-PVAT 0.85.±0.11 (n=8), +PVAT 0.88±0.15 (n=8)). Incubation with L-NNA prevented the anti-contractile effect of PVAT at 3 months (+PVAT/+L-NNA +1.09±0.36 (n=4)). At 24 months, incubation with L-NNA had no effect on contractility (+PVAT/+L-NNA +0.64±0.28 (n=7)) in either the presence of absence of PVAT. Summary: The anti-contractile effect of PVAT is lost with age in rats, due at least in part to a reduced bioavailability of NO. Further studies are currently being undertaken to further investigate the mechanisms involved.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCC407
Poster Communications: Aging modulates the anti-contractile effects of perivascular adipose tissue; the role of nitric oxide.
H. M. Melrose1, A. Heagerty1, G. Edwards1, C. Austin1
1. FMHS, University of Manchester, Manchester, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.