Browsing by Author "Goulopoulou, Styliani PhD"
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Item L-sulforaphane Decreased Contractile Response in Mesenteric Arteries in A Rat Model of Gestational Hypertension(2017-03-14) Osikoya, Oluwatobiloba; Goulopoulou, Styliani PhD; Cushen, SpencerBackground: Maternal hypertension is a state of inflammation characterized by oxidative stress. Exposure of pregnant rats to the Toll-like Receptor 9 activator, ODN2395, induces hypertension and upregulates vascular oxidative stress. The transcription factor, Nuclear Factor Erythroid 2 Like 2 (Nrf2), is a regulator of antioxidant response, is overexpressed in placentas from patients with preeclampsia. However, the role of Nrf2 in maternal vascular dysfunction is unknown. Hypothesis: L-sulforaphane, an Nrf2 activator, will have anti-contractile effects on arteries from pregnant rats treated with CpG oligonucleotides (a model of gestational hypertension). Methods: Pregnant Sprague-Dawley rats were treated with synthetic unmethylated CpG oligonucleotides (ODN2395, 100µg/intraperitoneal injection) or saline (Control) on gestational day 14, 16, and 18 (term=21-22 days). Blood pressure was measured before pregnancy and on gestational day 19 using the tail cuff method. The contractile responses of mesenteric resistance arteries to a thromboxane A2 (TxA2) mimetic, U46619, in the presence or absence of Nrf2 activator, L-sulforaphane (L-S, 40 µM), were assessed by wire myography on gestational day 21. Results: Rats treated with ODN2395 had greater systolic blood pressure on gestational day 19 compared to control rats (Control, n=9: 100±4 mmHg vs. ODN2395, n=7: 119±4 mmHg, p=0.007). Three-hour but not one-hour incubation with L-sulforaphane reduced the contractile response to U46619 in mesenteric arteries from both ODN2395 and control rats (Peak contraction as %Max KCl (120mM), Control Veh: 120.5%±4.85; Control L-S: 39.1%±7.16; ODN2395 Veh: 111.1%±4.19; ODN2395 L-S: 42.6%±2.68). Conclusions: Pregnancy is a state of oxidative stress and this may explain the anti-contractile effects of L-sulforaphane in arteries from normal, healthy rats. In preeclampsia, levels of oxidative stress are greater compared to normotensive pregnancies and thus, systemic treatment with L-sulforaphane or other Nrf2 activators may improve poor cardiovascular outcomes in pregnancies with preeclampsia.Item Low-dose Aspirin During Gestation Promotes Vascular Dysfunction and does not Ameliorate Maternal Hypertension in Rats Exposed to Innate Immune System Activation(2016-03-23) Nguyen, An; Valdes, Melissa; Osikoya, Oluwatobiloba; Goulopoulou, Styliani PhD; Jaini, PareshBackground: Daily low-dose aspirin after 12 weeks of gestation is recommended as a preventive intervention for women at high risk for preeclampsia, a hypertensive disorder of pregnancy with high rates of maternal and fetal mortality and morbidity. Activation of the innate immune system during pregnancy is implicated in the development of preeclampsia. Maternal exposure to synthetic CpG oligonucleotides (CpG ODN, specific ligand of the innate immune receptor Toll-like receptor 9) induces maternal hypertension, vascular dysfunction, and upregulation of cyclooxygenase enzymes in pregnant rats. Hypothesis: We hypothesized that maternal treatment with low-dose aspirin during gestation would ameliorate TLR9-induced hypertension and vascular dysfunction in pregnant rats. Methods: Pregnant Sprague-Dawley rats were treated with a synthetic CpG ODN (ODN2395) or vehicle on gestational day (GD) 14, 16, and 18. Aspirin treatment (or control) started on GD10 and continued throughout gestation for all groups [control (no treatment), ODN2395 (300 μg), aspirin (1.5 mg/kgBW), aspirin+ODN2395]. Blood pressure was measured on GD19 using the tail cuff method and mesenteric resistance artery (MES) function was assessed on GD21 using wire myography. Results: ODN2395-treated rats had higher blood pressure on GD19 compared to vehicle-treated dams and aspirin did not ameliorate ODN2395-induced hypertension (control: 97 ± 0.4 mmHg, ODN2395: 121 ± 7 mmHg, aspirin: 101 ± 5 mmHg, aspirin+ODN2395: 121 ± 7 mmHg, p Aspirin treatment increased MES sensitivity to PE (pEC50, ODN2395: 5.6 ± 0.1 vs. aspirin+ODN2395: 5.9 ± 0.1, ppEC50, ODN2395: 7.6 ± 0.1 vs. aspirin+ODN2395: 7.0 ± 0.1, pConclusion: Treatment with low-dose aspirin throughout gestation did not prevent the development of TLR9-induced maternal hypertension, augmented vascular sensitivity to α1-adrenergic receptor activation and attenuated endothelium-dependent dilation in rats exposed to innate immune system activation. The use of aspirin during gestation should be considered with caution in clinical cases associated with innate immune system-induced pregnancy complications.Item Multiparity has beneficial effects on vascular function in an experimental model of type 2 diabetes(2016-03-23) Hannan, Johanna; Webb, R.; Goulopoulou, Styliani PhD; Posey, RachelBackground: Correlational studies have showed that parity is associated with risk for cardiovascular disease (CVD). According to these correlations, multiparous women have reduced risk of developing CVD compared to nulliparous women. Experimental studies examining the effects of parity on vascular function are lacking and most importantly, how parity affects women with established cardiovascular risk factors is unknown. Women with type 2 diabetes have a greater risk of developing vascular complications compared to their non-diabetic counterparts. This study focuses on the influence of parity on contractile arterial responses of multiparous and nulliparous rats with type 2 diabetes. Hypothesis: Old multiparous rats with type 2 diabetes (Goto-Kakizaki rats, GK) were hypothesized to have a decreased contractile response to phenylephrine (PE) and endothelin-1 (ET-1) compared to nulliparous GK young and age-matched rats. Materials and Methods: Three experimental groups were used: GK young nulliparous rats, 20 weeks old (GK Young NP); GK old nulliparous rats, 60 weeks old (GK Old NP); and GK old multiparous rats, 60 weeks old (GK Old MP). Mesenteric resistance arteries (MA) were mounted in a wire myograph to measure the contractile responses to PE (10-9 – 3x10-5 M) and ET-1 (10-11 – 10-7 M). Results: GK Old MP rats were heavier compared to GK Old and GK Young NP rats (297 ± 7 g vs. 255 ± 11 g vs. 232 ± 4 g, p0.05). Mesenteric arteries from GK Old MP rats had reduced sensitivity (-logEC50) to ET-1 compared to arteries from GK Old NP and GK Young NP groups (7.82 ± 0.11 vs. 8.45 ± 0.08 vs. 8.24 ± 0.07, p Conclusions: Nulliparity may have adverse effects on vascular function in women with type 2 diabetes. Taking a parity history may be beneficial when evaluating women with type 2 diabetes for risk of developing CVD.Item Uterine Perivascular Adipose Tissue Potentiates Contractile Responses in Uterine Arteries from Pregnant rats(2016-03-23) Goulopoulou, Styliani PhD; Osikoya, OluwatobilobaBackground: 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.