Abstract
Perivascular adipose tissue (PVAT) can regulate vascular tone. In mesenteric arteries of SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP.ZF) with metabolic syndrome, vascular dysfunction is compensated by PVAT-dependent mechanisms that disappear with increasing age. In this study, we investigated the mechanisms of the age-related changes and responsible factor(s) involved in the enhancing effects of mesenteric arterial PVAT in SHRSP.ZF. Acetylcholine- and sodium nitroprusside-induced relaxations of isolated arteries were greater with PVAT than without PVAT at 17 and 20 weeks of age (wks), and as expected, this enhancement by the presence of PVAT disappeared at 23 wks. PVAT mRNA levels of angiotensin II type 1 (AT1) receptor-associated protein was less and AT1 receptor was unchanged at 23 wks when compared to 20 wks. At 20 wks, the enhanced acetylcholine-induced relaxation by the presence of PVAT was inhibited by N-acetyl-l-cysteine (NAC). Acetylcholine-induced relaxation of arteries without PVAT was increased in the presence of exogenously added apelin. PVAT mRNA level of apelin was higher in SHRSP.ZF than in control Wistar-Kyoto rats, and the level was decreased with aging. These results suggest that AT1 receptor activation in PVAT, and changes in the regulation of apelin and a NAC-sensitive factor are related to the age-dependent deterioration of the vasodilation enhancing effects of mesenteric arterial PVAT in SHRSP.ZF.
Highlights
The perivascular adipose tissue (PVAT), located on the outside of blood vessels, has been recognized to regulate vascular tone and wall remodeling via the release of several bioactive substances, adipokines, resulting in the development of cardiovascular disease due to metabolic syndrome (MetS) [1,2]
We proposed to test whether AT1 receptor-associated protein (ATRAP), and angiotensin II (Ang II) type 1 (AT1) mRNA expressions in PVAT are altered with aging in SHRSP.ZF
To assess the mechanisms underlying the disappearance of PVAT functions, we investigated whether mRNA transcripts of AT1 receptor and ATRAP in mesenteric arterial PVAT are changed with increasing age in SHRSP.ZF
Summary
The perivascular adipose tissue (PVAT), located on the outside of blood vessels, has been recognized to regulate vascular tone and wall remodeling via the release of several bioactive substances, adipokines, resulting in the development of cardiovascular disease due to metabolic syndrome (MetS) [1,2]. 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. The enhancing effects by PVAT of SHRSP.ZF mesenteric arteries are inhibited by treatment with L-NAME or removing the endothelium [4]. We hypothesized that HNO, generated from NO and H2S, contributes to the enhancing effects of mesenteric arterial PVAT on vasodilation in the MetS rats. As an initial test of the nitroxyl hypothesis, we assessed whether NAC inhibited the PVAT enhancing effects in SHRSP.ZF mesenteric artery. Based on the results of our study, we provide evidence to identify important factor(s) responsible for the compensatory effects of mesenteric arterial PVAT under the condition of vascular dysfunctions in MetS
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