Uterine Perivascular Adipose Tissue Potentiates Contractile Responses in Uterine Arteries from Pregnant rats

Background: Perivascular adipose tissue (PVAT) is the fourth and outer layer of the vascular wall. PVAT has vasoactive effects, mostly via paracrine actions. The effects of PVAT vary with anatomic location; PVAT has anti-contractile effects in peripheral vascular beds in animals and in humans but it potentiates contractions in coronary vascular smooth muscle. Pregnancy is characterized by adipose tissue expansion as well as structural and functional changes in the uterine vasculature. However, the effects of PVAT on uterine artery reactivity during pregnancy are not understood. Hypothesis: We hypothesized that uterine PVAT has a functional role in uterine artery contractile and dilatory responses and this role is modified by pregnancy. Methods: Pregnant Sprague-Dawley rats were sacrificed on gestational day 16 (term=21-22 days). Uterine arteries and their surrounding PVAT were harvested and cleaned for study. Concentration response curves (CRCs) to potassium chloride (KCl, 4.7 – 80 mM) and phenylephrine (PE, 10-9 - 3x10-5 M) were performed using wire myography. CRCs were performed in the presence and absence of the surrounding PVAT (0.1 g) or PVAT-conditioned media. Arteries were incubated with PVAT or PVAT-conditioned media for 30 minutes. To make the media, we incubated 0.4 g of PVAT in 15 ml physiological salt solution for 90 min (37oC - 5% CO2, 95% O2). Results: Uterine arteries incubated with PVAT (+PVAT) had greater contractile responses to KCl compared to control vessels [KCl (30 mM), control: 4.0 ± 0.81 mN vs. +PVAT: 14.7 ± 1.68 mN; KCl (40 mM), control: 14.4 ± 0.68 mN vs. +PVAT: 19.6 ± 0.88 mN, p50, control: 6.0 ± 0.08 vs. +PVAT: 6.3 ± 0.10, p50), control: 6.1 ± 0.08 vs. +PVAT-media: 6.4 ± 0.10, p=0.07]. Conclusions: Our data show that uterine PVAT has a pro-contractile effect on uterine arteries from pregnant rats. We propose that uterine PVAT provides signaling from the outer layer to the inner layers of the vascular wall that determines uteroplacental vascular adaptations to pregnancy.