Resistance Arteries from Low‐Capacity Running Rats Exhibit Diminished Acetylcholine‐Induced Relaxation in Comparison to High‐Capacity Running Rats: Effects of Native and Allografted Perivascular Adipose Tissue on Vascular Function

Abstract

Previous research has demonstrated that perivascular adipose tissue (PVAT) plays a significant metabolic role in vascular function by secreting a variety of bioactive substances in both healthy and diseased states. PVAT has been largely recognized to cause an anti‐contractile response; this anti‐contractile action is lost in cardiovascular diseases, including hypertension. Acknowledging the importance of PVAT in vascular health, we hypothesized that the impact of PVAT on vascular function would be different in healthy and diseased states. Specifically, we investigated the potential therapeutic and harmful effects of native PVAT and allografted PVAT on vascular function from an animal model of metabolic syndrome compared to an animal model for longer lifespan. Our animal model (male, 20–24‐weeks old) study used low‐capacity running rats (LCR) as a model for metabolic syndrome, high‐capacity running rats (HCR) as a model for an “ultra‐healthy” state and high response trainer rats (HRT) served as a control. The intrinsic and trained aerobic capacity of HRT rats is higher than LCR rats but lower than HCR rats. Mesenteric resistance arteries (MRA) and MRA PVAT from HRT rats, LCR rats, and HCR rats were extracted. The MRA were isolated and mounted in a wire myograph. Concentration‐response curves to acetylcholine (1nM – 30μM) were performed in the absence and presence of an animal's native mesenteric PVAT or LCR/HCR grafted mesenteric PVAT. T‐test *p < 0.05; n=3–4. We observed a dramatic change in PVAT structure between control, LCR, and HCR animals (Figure 1). The efficacy of acetylcholine, an endothelium‐dependent vasodilator of MRA, was diminished in LCR rats compared to HRT rats and HCR rats (Emax: HRT: 97.88 ± 0.8314 vs. LCR: 77.43 ± 7.038* vs. HCR: 97.70 ± 1.942, p < 0.05). As has been previously shown, the presence of native PVAT increased the HRT MRA sensitivity to acetylcholine‐induced relaxation. However, the presence of native PVAT diminished the LCR MRA sensitivity to acetylcholine‐induced relaxation. This sensitivity was restored by allografting HCR PVAT onto the LCR MRA. Although no changes were observed in HCR MRA relaxation in the presence of its native PVAT, allografting LCR PVAT onto the HCR MRA decreased the HCR MRA relaxation. This data suggests that LCR rats present with an impaired PVAT that contributes to diminished vascular relaxation. On the other hand, HCR rats present with an enhanced PVAT that could potentially improve vascular relaxation. This study demonstrates the potential therapeutic effect of PVAT from HCR rats.Support or Funding InformationThis work was supported by National Institutes of Health (NIH) (NIGMS: K99GM11888).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.