Abstract

Chemical signals from perivascular adipose tissue (PVAT) modulate the structure and function of blood vessels. This may be partially under sympathetic neural control, however, little is known about the density of sympathetic innervation of PVAT. We hypothesized sympathetic nerve (SN) density in PVAT surrounding mesenteric resistance arteries (MRAs) is similar to that in the adventitia of the MRAs, and that high-fat feeding (HFF, 16 weeks) would decrease the density of SNs on MRAs and in PVAT. To test these hypotheses, we labeled SNs on MRAs and in PVAT with rabbit anti-tyrosine hydroxylase (TH) antibodies/AlexaFluor488-conjugated donkey-anti-rabbit antibodies, ex vivo. TH staining density (fraction occupied by TH-labeled structures) was computed from thresholded, background subtracted, maximum intensity z-projections of image stacks. TH staining density was higher at the surface of MRAs (0.21±0.03, n = 14) than within PVAT (0.013±0.003, n = 42, p<0.0001, Fig. 1 - arrows point to TH-positive nerves). HFF increased PVAT adipocyte diameter from 39±0.5μm (n=672) to 72±0.6μm (n = 365, p<0.0001). However, HFF had no effect on TH staining density on MRAs or within PVAT (p=0.83). Thus, while MRA’s are robustly innervated by SNs, only the first layer of adipocytes adjacent to MRA adventitia is exposed to a similar SN density; SN density in PVAT more than one adipocyte away from MRAs is >16 fold lower. HFF does not affect SN density on MRAs or in PVAT. However, given the larger size of adipocytes in HFF rats, this may mean an increase in SN density/adipocyte. Nonetheless, the low density of SNs in mesenteric PVAT suggests limited direct SN control of PVAT function in the bulk of PVAT adipocytes.

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