Abstract 260: Aging Decreases the Anticontractile Effect of Perivascular Adipose Tissue in the Mouse Aorta

Abstract

The perivascular adipose tissue (PVAT) exerts an anticontractile effect via paracrine release of bioactive molecules. During vascular dysfunction associated with hypertension and obesity the anticontractile effect of PVAT is reduced or lost. Although vascular dysfunction associated with aging is well documented, there are no studies investigating whether PVAT plays a role in this context. We hypothesized that the PVAT anticontractile effect would be reduced with age. Mouse aorta from 3 and 9 month-old male C57bl6 mice was used in contractility experiments in the presence and absence of PVAT. Contractile responses to phenylephrine (PE) and serotonin (5-HT) were reduced in the presence of PVAT in both age groups (pD2 PE: young-PVAT=7.13±0.09, young+PVAT=6.24±0.09, old-PVAT=6.96±0.12, old+PVAT=6.49±0.18; pD2 5-HT: young-PVAT=6.74±0.08, young+PVAT=5.98±0.16, old-PVAT=6.58±0.08, old+PVAT=6.29±0.09). Relaxation responses to acetylcholine were not significantly changed by PVAT in either group. Despite an increased PVAT mass in the older mice, the magnitude of the anticontractile effect of PVAT was reduced in older compared to younger mice (% reduction PE contraction: young=66.6±7.8, old=49,1±15.4; % reduction 5-HT contraction: young=55.5±15.1, old=31.9±9.1). Inhibition of cystathionine gamma lyase (CSE), a hydrogen sulfide synthesizing enzyme, did not reverse the reduced 5-HT-induced contraction in PVAT intact aorta in either group. Our results show that the anticontractile effect of PVAT is reduced with age, potentially contributing to the vascular dysfunction observed in aging.