Testosterone alters maternal vascular adaptations: Role of the endothelial no system

Vijayakumar Chinnathambi, Meena Balakrishnan, Jayanth Ramadoss, Chandrasekhar Yallampalli, Kunju Sathishkumar

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    Abstract

    Sex steroid hormones estradiol and progesterone play an important role in vascular adaptations during pregnancy. However, little is known about the role of androgens. Plasma testosterone (T) levels are elevated in preeclampsia, mothers with polycystic ovary, and pregnant African American women, who have endothelial dysfunction and develop gestational hypertension. We tested whether increased T alters vascular adaptations during pregnancy and whether these alterations depend on endothelium-derived factors, such as prostacyclin, endothelium-derived hyperpolarizing factor, and NO. Pregnant Sprague Dawley rats were injected with vehicle (n=12) or T propionate [0.5 mg/Kg per day from gestation day 15-19; n=12] to increase plasma T levels 2-fold, similar to that observed in preeclampsia. Telemetric blood pressures and endothelium-dependent vascular reactivity were assessed with wire-myograph system. Phospho-endothelial NO synthase and total endothelial NO synthase were examined in mesenteric arteries. Mean arterial pressures were significantly higher starting from gestation day19 until delivery in T-treated dams. Endothelium-dependent relaxation responses to acetylcholine were significantly lower in mesenteric arteries of T-treated dams (pD2 [-log EC50]=7.05±0. 06; Emax=89.4±1.89) compared with controls (pD2=7.38±0.04; Emax=99.9±0.97). Further assessment of endothelial factors showed NO-mediated relaxations were blunted in T-treated mesenteric arteries (Emax=42.26±5.95) compared with controls (Emax=76.49±5.06); however, prostacyclin-and endothelium-derived hyperpolarizing factor-mediated relaxations were unaffected. Relaxation to sodium nitroprusside was unaffected with T-treatment. Phosphorylations of endothelial NO synthase at Ser were decreased and at Thr increased in T-treated mesenteric arteries without changes in total endothelial NO synthase levels. In conclusion, increased maternal T, at concentrations relevant to abnormal clinical conditions, cause hypertension associated with blunting of NO-mediated vasodilation. T may induce the increased vascular resistance associated with pregnancy-induced hypertension.

    Original languageEnglish (US)
    Pages (from-to)647-654
    Number of pages8
    JournalHypertension
    Volume61
    Issue number3
    DOIs
    StatePublished - Mar 2013

    Fingerprint

    Mesenteric Arteries
    Nitric Oxide Synthase
    Endothelium
    Blood Vessels
    Testosterone
    Mothers
    Pregnancy
    Pregnancy Induced Hypertension
    Epoprostenol
    Pre-Eclampsia
    Propionates
    Vascular Endothelium
    Gonadal Steroid Hormones
    Nitroprusside
    Vasodilation
    African Americans
    Vascular Resistance
    Androgens
    Acetylcholine
    Progesterone

    Keywords

    • blood pressure
    • endothelium-derived hyperpolarizing factor
    • eNOS phosphorylation
    • hypertension
    • mesenteric arteries
    • prostacyclin
    • vasodilation

    ASJC Scopus subject areas

    • Internal Medicine

    Cite this

    Chinnathambi, V., Balakrishnan, M., Ramadoss, J., Yallampalli, C., & Sathishkumar, K. (2013). Testosterone alters maternal vascular adaptations: Role of the endothelial no system. Hypertension, 61(3), 647-654. https://doi.org/10.1161/HYPERTENSIONAHA.111.00486

    Testosterone alters maternal vascular adaptations : Role of the endothelial no system. / Chinnathambi, Vijayakumar; Balakrishnan, Meena; Ramadoss, Jayanth; Yallampalli, Chandrasekhar; Sathishkumar, Kunju.

    In: Hypertension, Vol. 61, No. 3, 03.2013, p. 647-654.

    Research output: Contribution to journalArticle

    Chinnathambi, V, Balakrishnan, M, Ramadoss, J, Yallampalli, C & Sathishkumar, K 2013, 'Testosterone alters maternal vascular adaptations: Role of the endothelial no system', Hypertension, vol. 61, no. 3, pp. 647-654. https://doi.org/10.1161/HYPERTENSIONAHA.111.00486
    Chinnathambi V, Balakrishnan M, Ramadoss J, Yallampalli C, Sathishkumar K. Testosterone alters maternal vascular adaptations: Role of the endothelial no system. Hypertension. 2013 Mar;61(3):647-654. https://doi.org/10.1161/HYPERTENSIONAHA.111.00486
    Chinnathambi, Vijayakumar ; Balakrishnan, Meena ; Ramadoss, Jayanth ; Yallampalli, Chandrasekhar ; Sathishkumar, Kunju. / Testosterone alters maternal vascular adaptations : Role of the endothelial no system. In: Hypertension. 2013 ; Vol. 61, No. 3. pp. 647-654.
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