An adrenergic system in PVAT

Using HPLC, we have discovered time and again that the PVATs around rodent and human blood vessels contains significant amounts of amines, especially norepinephrine (NE), the neurotransmitter of the sympathetic nervous system.  Importantly, these catecholamines are vasoactive, meaning that if we stimulate their release, they cause vascular contraction!  As such, the fat living right outside the vessel is poised to change how the vessel functions, and this is relevant to CV disease.  Our goal is to determine whether a true adrenergic system (synthesis, storage, release and uptake) of NE exists in PVAT, and how this changes in obesity associated hypertension.  The references in (A) supports the existence and release of functional catecholamines as facilitated by organic cation transporter 3 (B). The predominant release of NE over 5-HT was validated with use of fenfluramine (C), and Maleeha Ahmad, Nadia Sayal-Lopez, Emma Darios, Alex Ismail, Robert Burnett and Arun Anantharam were the first to demonstrate functional VMAT vesicles in the adipocytes of PVAT (D).

a. Ayala-Lopez, N, Martini M, Jackson W F, Darios E, Burnett R, Mahon B, Fink, G. D. and Watts, S. W.: Perivascular adipose tissue contains functional catecholamines.  Pharmacology Research and Perspectives, Volume 2, Issue 3, June 2014.  PMCID:PMC4041285. 

b. Ayala-Lopez, N., Jackson, W. F., Burnett, R., Wilson, J. N. and Watts, S. W.: Organic cation transporter-3 contributes to norepinephrine uptake in perivascular adipose tissue, Am J Physiol Heart Circ Physiol, 309:H1904-1914, 2015.

C. Kumar R. K., Darios, E. S., Burnett, R. and Watts, S. W.: Fenfluramine-induced PVAT-dependent contraction of rat aorta depends on norepinephrine and not serotonin, Pharmacol Res, 140:43-49, 2019.      

D. Ahmad, M., Ayala-Lopez, N., Darios, E; Ismail, A, Ferland, D., Burnett, R., Anantharam, A. and Watts, S. W. Perivascular adipocytes store norepinephrine by vesicular transport, Art. Thromb. Vasc. Biol., 39:188-199, 2019.