Uterine perivascular adipose tissue is a novel mediator of uterine artery blood flow and reactivity in rat pregnancy

Abstract

Key pointsr In vivo, uterine perivascular adipose tissue (PVAT) potentiates uterine artery blood flow in pregnant rats, although not in non-pregnant rats.r In isolated preparations, uterine PVAT has pro-contractile and anti-dilatory effects on uterine arteries.r Pregnancy induces changes in uterine arteries that makes them responsive to uterine PVAT signalling.Abstract An increase in uterine artery blood flow (UtBF) is a common and necessary feature of a healthy pregnancy. In the present study, we tested the hypothesis that adipose tissue surrounding uterine arteries (uterine perivascular adipose tissue; PVAT) is a novel local mediator of UtBF and uterine artery tone during pregnancy. In vivo experiments in anaesthetized Sprague-Dawley rats showed that pregnant animals (gestational day 16, term = 22--23 days) had a three-fold higher UtBF compared to non-pregnant animals. Surgical removal of uterine PVAT reduced UtBF only in pregnant rats. In a series of ex vivo bioassays, we demonstrated that uterine PVAT had pro-contractile and anti-dilatory effects on rat uterine arteries. In the presence of PVAT-conditioned media, isolated uterine arteries from both pregnant and non-pregnant rats had reduced vasodilatory responses. In non-pregnant rats, these responses were mediated at the level of uterine vascular smooth muscle, whereas, in pregnant rats, PVAT-media reduced endothelium-dependent relaxation. Pregnancy increased adipocyte size in ovarian adipose tissue but had no effect on uterine PVAT adipocyte morphology. In addition, pregnancy down-regulated the gene expression of metabolic adipokines in uterine but not in aortic PVAT. In conclusion, this is the first study to demonstrate that uterine PVAT plays a regulatory role in UtBF, at least in part, as a result of its actions on uterine artery tone. We propose that the interaction between the

Cyclooxygenase-dependent mechanisms mediate in part the anti-dilatory effects of perivascular adipose tissue in uterine arteries from pregnant rats

“…The reduction in UtBF following removal of PVAT was not observed in non-pregnant rats (41), suggesting that the interaction between PVAT and uterine artery is pregnancy-specific. In vascular preparations of isolated uterine arteries from pregnant rats, PVAT suppressed uterine artery relaxation to acetylcholine (ACh), and this anti-dilatory effect was mediated by soluble factors secreted by uterine PVAT (41). These previous in vivo studies demonstrated the functional role of PVAT in the uterine vasculature in rat pregnancy, while the in vitro studies interrogated the effects of PVAT on the uterine vascular wall in the absence of systemic and hemodynamic factors.…”

“…Functional bioassays were used to determine vascular release of TxA2 and PGI2. PVAT was used to prepare PVAT-conditioned media (PVATmedia) as previously described (41). Briefly, PVATmedia was prepared by incubating 0.4 mg of uterine PVAT in 15 mL Krebs-Henseleit solution, which was continuously gassed with 95% O2 and 5% CO2.…”

“…Briefly, PVATmedia was prepared by incubating 0.4 mg of uterine PVAT in 15 mL Krebs-Henseleit solution, which was continuously gassed with 95% O2 and 5% CO2. Following 1 hour incubation in Krebs-Henseleit solution, PVATmedia was filtered with a 0.20 µm syringe filter (cat#: 431222, Corning Life Sciences, Corning, NY) and the filtrate was added to the myograph chambers for vascular reactivity experiments used for uterine artery stimulation (41).…”

“…Myograph chambers were filled with Krebs-Henseleit solution (37 o C), which was continuously gassed with 95% O2 and 5% CO2. Optimal baseline tension was determined for each individual vascular segment using the DMT Normalization Module for LabChart Software (ADInstruments, Colorado Springs, CO) as previously described (41,42). Vessels were allowed to equilibrate for 1 hour at baseline tension.…”

“…Perivascular adipose tissue (PVAT) is a metabolically active and physiologically relevant tissue that contributes to the maintenance of vascular homeostasis by modulating vascular tone (1, 2,4,7,35,41). The effects of PVAT on its adjacent vascular wall are either due to uptake and metabolism of vasoactive amines from nerves innervating blood vessels by PVAT (57) or by direct action of PVAT-derived factors (4,18,31) on vascular smooth muscle and endothelial cells (3,44).…”