Time-Dependent Differences in the Influence of Perivascular Adipose Tissue on Vasomotor Functions in Metabolic Syndrome

Abstract

PVAT may regulate arterial tone by releasing diffusible vasorelaxing factor(s), which, through endothelium-derived NO production, compensates for impaired vasodilations at early stages of MetS.

Perivascular Adipose Tissue-Enhanced Vasodilation in Metabolic Syndrome Rats by Apelin and N-Acetyl–l-Cysteine-Sensitive Factor(s)

“…Similarly, sodium nitroprusside-induced relaxations were enhanced by the presence of PVAT at 17 and 20 wks, but were not altered at 23 wks. These results were consistent with our previous observations that PVAT enhanced vasodilations in response to not only endogenous NO, but also exogenous NO in mesenteric artery of SHRSP.ZF [4]. Interestingly, the time-course for disappearance of PVAT functions followed the time-course of worsening metabolic parameters described above.…”

“…MetS is a chronic condition which worsens with time and thus, requires long-term strategies for clinical treatment. Our previous studies show that mesenteric PVAT has compensatory effects to maintain vascular tonus under the condition of impaired NO-mediated relaxations in SHRSP.ZF (at 20 wks), i.e., PVAT enhances vasodilation in response to either endothelium-derived NO induced by acetylcholine or exogenous NO derived from sodium nitroprusside in mesenteric artery of SHRSP.ZF [4,30,31]. However, the compensatory function of PVAT was impaired at a later stage of MetS (at 30 wks).…”

“…These results suggest that AT1 receptor activity in PVAT is related to the deterioration of the enhancing effects of PVAT on vascular relaxations. Since the breakdown of the PVAT enhancing effect is observed later in the time-course of MetS (at 30 wks) [4], PVAT dysfunction, probably, occurs around 23 wks in the aging process in SHRSP.ZF with MetS. On the other hand, apelin mRNA in mesenteric PVAT was higher in SHRSP.ZF than controls and the incubation of tissues with exogenous apelin resulted in enhanced acetylcholine-induced relaxations.…”

“…Therefore, we have assessed the role of PVAT in vascular dysfunctions using SHRSP.Z- Lepr fa /IzmDmcr rats (SHRSP.ZF), which were established as an animal model of MetS by crossing stroke-prone spontaneously hypertensive rats of the Izumo strain (SHRSP/Izm) to Zucker-fatty rats [3]. We proposed that PVAT plays a role in retaining vascular tonus under the conditions of vascular dysfunctions in response to nitric oxide (NO), and this compensatory system of PVAT will breakdown later in the time-course of MetS [4]. However, the identities of the PVAT-dependent factor(s) that enhance vasodilations and regulate the development and/or breakdown of the compensatory effects of PVAT in SHRSP.ZF with MetS are undetermined.…”

“…Vasodilation induced by a H 2 S donor was observed in samples of human mesenteric artery and this vasodilation was reduced by treatment with an inhibitor of NO synthase, l -NAME, or endothelium removal [23]. Interestingly, the enhancing effects by PVAT of SHRSP.ZF mesenteric arteries are inhibited by treatment with l -NAME or removing the endothelium [4]. It has been proposed that a reaction product of a chemical reaction between H 2 S and S -nitrosoglutathione, a so-called NO donor, putatively generates nitroxyl anions, likely in the more stable HNO form, and is involved in the relaxation of isolated rat thoracic aortas and mesenteric artery [24].…”