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L‐Sulforaphane Decreased Contractile Response in Mesenteric Arteries in a Rat Model of Gestational Hypertension
Author(s) -
Cushen Spencer C,
Osikoya Oluwatobiloba,
Goulopoulou Styliani
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1011.19
Subject(s) - sulforaphane , medicine , endocrinology , oxidative stress , mesenteric arteries , vasoconstriction , preeclampsia , pregnancy , biology , artery , cancer research , genetics
Background 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, which 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 A 2 (TxA 2 ) 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 Dams 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). One‐hour incubation with L‐sulforaphane did not affect contractile responses to U46619 in arteries from control or ODN2395‐treated rats. Incubation with L‐sulforaphane for 3 hours 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). Conclusion 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. Support or Funding Information University of North Texas Health Science Center; American Heart Association