Abstract 119: Norepinephrine (NE) Resides in Renal Perivascular Adipose Tissue: Form and Function

Abstract

Perivascular adipose tissue (PVAT) is gaining importance as its ability to secrete and take up substances that modify vascular tone, and thus blood pressure. The kidney is inarguably important to blood pressure regulation, but little is known about renal arterial PVAT (RP) relative to its adipogenic profile or its function to modify arterial contraction as specifically conducted by a resident adrenergic system. We hypothesized that NE was present in RP, that RP had a mixture of both brown and white adipocyte gene signatures and that the NE in RP could promote renal artery contraction. Our model was the isolated renal artery +/- PVAT of the male Sprague Dawley rat, with thoracic aortic PVAT (TAP) and mesenteric PVAT (MP) as brown-like and white fat comparators, respectively. HPLC and immunohistochemistry (IHC) were used to detect NE; RT-PCR to construct an adipogenic/adrenergic profile; and myography to measure contraction. All PVATs contained NE (ng/g tissue, n=4-6): RP:524±68, TAP:740±16, MP:96±24. In RP, NE, visualized by IHC, was clearly present in adipose tissue resembling both brown and white fat. The identification of brown fat was validated by positive uncoupling protein-1 (UCP-1) staining in the RP; this made up some but not all of the RP. RT-PCR measures (2-ddCt values, n=4) supported expression of both brown-like (UCP-1: RP: 1.0±0.1, MP 3.2e-05±2.94e-05, TAP: 1.3±0.1; Cidea: RP: 1.0±0.1, MP: 0.01±0.002, TAP: 0.9±0.1) and white adipogenic genes (Tcf21: RP: 1.0±0.2, MP: 5.9±1.0, TAP: 0.3±0.1). The existence of a functional adrenergic system in the RP was supported by two findings. First, the efficacy of the indirect sympathomimetic tyramine to cause contraction was greater in isolated renal artery (n=11) +PVAT (14.4+1.8mN) vs -PVAT (7.6+1.2mN). Second, tyramine-induced contraction in +PVAT tissues was reduced by the α1-adrenoceptor antagonist prazosin (100 nM; 90+5%, n=6) and NE transporter inhibitor nisoxetine (1 uM; -logEC50 [M]- Veh: -5.0+0.4; nisoxetine = 3.7+0.2 n=4). Collectively, these data support the existence of a functional adrenergic system in a PVAT that has a profound potential to change renal arterial function. Knowledge about this fat depot may increase our ability to modify renal function in the treatment of hypertension.