Abstract 662: Perivascular Adipose Tissue-derived Prostaglandins Constrict Vessel
Background: Perivascular adipose tissue (PVAT) is associated with reduced response to vasoconstricting agents in the murine vasculature and also in human small arteries, and this anti-contractile effect is reduced in subjects with metabolic syndrome. However, it was suggested that other vasoconstrictors released from PVAT such as leptin or Angiotensin II causes vasoconstriction, suggesting that PVAT has contractile properties as well. Here we show that prostaglandins and adrenalin signaling derived from PVAT contribute to contractile properties of PVAT.
Results: The effect of donor PVAT on the vascular tone was evaluated in carotid, thoracic and mesenteric arteries using a myograph chamber in which the PVAT surrounding the tested vessel was completely removed. Fifteen mg of minced PVAT (size of ∼1 mm3) from donor C57BL/6J mice into the myograph chamber results in mild vasoconstriction (1.52±0.6mN) on carotid artery rings. This contractile property of PVAT is effective on vessel rings obtained from the thoracic aorta and mesenteric artery as well. PVAT from leptin knockout mice used as a donor causes vasoconstriction similar to that of wild-type mice (1.55±0.5mN leptin knockout vs. 1.52±0.6mN C57BL/6J mice). Pre-incubation of vessel rings with increasing concentrations of nonspecific COX inhibitor (10-9M to 10-6M indomethacin) inhibits PVAT-induced constriction in a dose-dependent manner (1.55±0.7mN, 1.41±0.6mN, 1.23±0.5mN, 0.95±0.4mN, 0.56±0.6mN, respectively), suggesting that PVAT-derived prostaglandin are responsible for vascular constriction. Similarly, pre-incubation with alpha-adrenergic receptor antagonists blocks PVAT-dependent vasoconstriction. Carotid artery responses to a series of 10-7M phenylephrine (PE) addition/wash out (5x) experiments in the myograph chamber cause alpha-adrenergic desensitization. However, in the presence of donor PVAT, carotid arteries have preserved maximal contraction after 5 rounds of PE addition/wash out experiments.
Conclusion: Our studies indicate that PVAT-derived prostaglandins rather than leptin or other adipokines cause vasoconstriction and reduce vascular alpha-adrenergic desensitization.
- © 2012 by American Heart Association, Inc.