Enhanced mesenteric arterial responsiveness to angiotensin II is androgen receptor-dependent in prenatally protein-restricted adult female rat offspring

Kunju Sathishkumar, Meena P. Balakrishnan, Chandrasekhar Yallampalli

    Research output: Contribution to journalArticle

    7 Citations (Scopus)

    Abstract

    Gestational protein restriction results in intrauterine growth restriction and hypertension in adult female growth-restricted rats. Enhanced vascular responsiveness to angiotensin II is observed, and blockade of the renin-angiotensin system abolishes hypertension in adult growth-restricted rats, suggesting that the renin-angiotensin system contributes to intrauterine growth restriction-induced hypertension. Moreover, growth-restricted adult rats have higher plasma testosterone levels, and antiandrogen treatment abolishes hypertension, indicating an important role for testosterone. We hypothesized that androgens may play a pivotal role in the enhanced responsiveness to Ang II and hypertension. Female offspring of pregnant rats fed 20% protein (control) or 6% protein diet (protein restricted), at 6 mo of age, were studied. Plasma testosterone and mean arterial pressure in protein-restricted offspring were significantly higher compared to controls. Flutamide treatment (10 mg/kg/day subcutaneously for 10 days) reduced mean arterial pressure in protein-restricted offspring but was without significant effect in controls. Vascular Agtr1/Agtr2 ratio was significantly higher in protein-restricted offspring, an effect that was reversed by flutamide. Flutamide treatment did not have any effect on Agtr1/Agtr2 ratio in controls. Enhanced contractile response to angiotensin II in mesenteric arteries was observed in protein-restricted offspring compared with control. Flutamide treatment reversed the enhanced contractile response to angiotensin II in protein-restricted offspring without significant effect in controls. Vascular reactivity to phenylephrine was similar between the control and protein-restricted offspring with and without flutamide treatment, suggesting that enhanced contractile response and flutamide's reversal effect is specific to angiotensin II. These results suggest that prenatally proteinrestricted rats exhibit an enhanced responsiveness to angiotensin II that is testosterone-dependent.

    Original languageEnglish (US)
    Article number55
    JournalBiology of Reproduction
    Volume92
    Issue number2
    DOIs
    StatePublished - Feb 1 2015

    Fingerprint

    Androgen Receptors
    Angiotensin II
    Flutamide
    Proteins
    Testosterone
    Hypertension
    Blood Vessels
    Growth
    Renin-Angiotensin System
    Arterial Pressure
    Therapeutics
    Androgen Antagonists
    Protein-Restricted Diet
    Mesenteric Arteries
    Phenylephrine
    Androgens

    Keywords

    • Agtr1
    • Angiotensin II
    • Blood pressure
    • Flutamide
    • Mesenteric arteries
    • Pregnancy
    • Protein restriction
    • Testosterone
    • Vascular function

    ASJC Scopus subject areas

    • Cell Biology

    Cite this

    Enhanced mesenteric arterial responsiveness to angiotensin II is androgen receptor-dependent in prenatally protein-restricted adult female rat offspring. / Sathishkumar, Kunju; Balakrishnan, Meena P.; Yallampalli, Chandrasekhar.

    In: Biology of Reproduction, Vol. 92, No. 2, 55, 01.02.2015.

    Research output: Contribution to journalArticle

    @article{cddfb0a8c7ed4b589f0de300aef85bfb,
    title = "Enhanced mesenteric arterial responsiveness to angiotensin II is androgen receptor-dependent in prenatally protein-restricted adult female rat offspring",
    abstract = "Gestational protein restriction results in intrauterine growth restriction and hypertension in adult female growth-restricted rats. Enhanced vascular responsiveness to angiotensin II is observed, and blockade of the renin-angiotensin system abolishes hypertension in adult growth-restricted rats, suggesting that the renin-angiotensin system contributes to intrauterine growth restriction-induced hypertension. Moreover, growth-restricted adult rats have higher plasma testosterone levels, and antiandrogen treatment abolishes hypertension, indicating an important role for testosterone. We hypothesized that androgens may play a pivotal role in the enhanced responsiveness to Ang II and hypertension. Female offspring of pregnant rats fed 20{\%} protein (control) or 6{\%} protein diet (protein restricted), at 6 mo of age, were studied. Plasma testosterone and mean arterial pressure in protein-restricted offspring were significantly higher compared to controls. Flutamide treatment (10 mg/kg/day subcutaneously for 10 days) reduced mean arterial pressure in protein-restricted offspring but was without significant effect in controls. Vascular Agtr1/Agtr2 ratio was significantly higher in protein-restricted offspring, an effect that was reversed by flutamide. Flutamide treatment did not have any effect on Agtr1/Agtr2 ratio in controls. Enhanced contractile response to angiotensin II in mesenteric arteries was observed in protein-restricted offspring compared with control. Flutamide treatment reversed the enhanced contractile response to angiotensin II in protein-restricted offspring without significant effect in controls. Vascular reactivity to phenylephrine was similar between the control and protein-restricted offspring with and without flutamide treatment, suggesting that enhanced contractile response and flutamide's reversal effect is specific to angiotensin II. These results suggest that prenatally proteinrestricted rats exhibit an enhanced responsiveness to angiotensin II that is testosterone-dependent.",
    keywords = "Agtr1, Angiotensin II, Blood pressure, Flutamide, Mesenteric arteries, Pregnancy, Protein restriction, Testosterone, Vascular function",
    author = "Kunju Sathishkumar and Balakrishnan, {Meena P.} and Chandrasekhar Yallampalli",
    year = "2015",
    month = "2",
    day = "1",
    doi = "10.1095/biolreprod.114.126482",
    language = "English (US)",
    volume = "92",
    journal = "Biology of Reproduction",
    issn = "0006-3363",
    publisher = "Society for the Study of Reproduction",
    number = "2",

    }

    TY - JOUR

    T1 - Enhanced mesenteric arterial responsiveness to angiotensin II is androgen receptor-dependent in prenatally protein-restricted adult female rat offspring

    AU - Sathishkumar, Kunju

    AU - Balakrishnan, Meena P.

    AU - Yallampalli, Chandrasekhar

    PY - 2015/2/1

    Y1 - 2015/2/1

    N2 - Gestational protein restriction results in intrauterine growth restriction and hypertension in adult female growth-restricted rats. Enhanced vascular responsiveness to angiotensin II is observed, and blockade of the renin-angiotensin system abolishes hypertension in adult growth-restricted rats, suggesting that the renin-angiotensin system contributes to intrauterine growth restriction-induced hypertension. Moreover, growth-restricted adult rats have higher plasma testosterone levels, and antiandrogen treatment abolishes hypertension, indicating an important role for testosterone. We hypothesized that androgens may play a pivotal role in the enhanced responsiveness to Ang II and hypertension. Female offspring of pregnant rats fed 20% protein (control) or 6% protein diet (protein restricted), at 6 mo of age, were studied. Plasma testosterone and mean arterial pressure in protein-restricted offspring were significantly higher compared to controls. Flutamide treatment (10 mg/kg/day subcutaneously for 10 days) reduced mean arterial pressure in protein-restricted offspring but was without significant effect in controls. Vascular Agtr1/Agtr2 ratio was significantly higher in protein-restricted offspring, an effect that was reversed by flutamide. Flutamide treatment did not have any effect on Agtr1/Agtr2 ratio in controls. Enhanced contractile response to angiotensin II in mesenteric arteries was observed in protein-restricted offspring compared with control. Flutamide treatment reversed the enhanced contractile response to angiotensin II in protein-restricted offspring without significant effect in controls. Vascular reactivity to phenylephrine was similar between the control and protein-restricted offspring with and without flutamide treatment, suggesting that enhanced contractile response and flutamide's reversal effect is specific to angiotensin II. These results suggest that prenatally proteinrestricted rats exhibit an enhanced responsiveness to angiotensin II that is testosterone-dependent.

    AB - Gestational protein restriction results in intrauterine growth restriction and hypertension in adult female growth-restricted rats. Enhanced vascular responsiveness to angiotensin II is observed, and blockade of the renin-angiotensin system abolishes hypertension in adult growth-restricted rats, suggesting that the renin-angiotensin system contributes to intrauterine growth restriction-induced hypertension. Moreover, growth-restricted adult rats have higher plasma testosterone levels, and antiandrogen treatment abolishes hypertension, indicating an important role for testosterone. We hypothesized that androgens may play a pivotal role in the enhanced responsiveness to Ang II and hypertension. Female offspring of pregnant rats fed 20% protein (control) or 6% protein diet (protein restricted), at 6 mo of age, were studied. Plasma testosterone and mean arterial pressure in protein-restricted offspring were significantly higher compared to controls. Flutamide treatment (10 mg/kg/day subcutaneously for 10 days) reduced mean arterial pressure in protein-restricted offspring but was without significant effect in controls. Vascular Agtr1/Agtr2 ratio was significantly higher in protein-restricted offspring, an effect that was reversed by flutamide. Flutamide treatment did not have any effect on Agtr1/Agtr2 ratio in controls. Enhanced contractile response to angiotensin II in mesenteric arteries was observed in protein-restricted offspring compared with control. Flutamide treatment reversed the enhanced contractile response to angiotensin II in protein-restricted offspring without significant effect in controls. Vascular reactivity to phenylephrine was similar between the control and protein-restricted offspring with and without flutamide treatment, suggesting that enhanced contractile response and flutamide's reversal effect is specific to angiotensin II. These results suggest that prenatally proteinrestricted rats exhibit an enhanced responsiveness to angiotensin II that is testosterone-dependent.

    KW - Agtr1

    KW - Angiotensin II

    KW - Blood pressure

    KW - Flutamide

    KW - Mesenteric arteries

    KW - Pregnancy

    KW - Protein restriction

    KW - Testosterone

    KW - Vascular function

    UR - http://www.scopus.com/inward/record.url?scp=84929574457&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84929574457&partnerID=8YFLogxK

    U2 - 10.1095/biolreprod.114.126482

    DO - 10.1095/biolreprod.114.126482

    M3 - Article

    C2 - 25550341

    AN - SCOPUS:84929574457

    VL - 92

    JO - Biology of Reproduction

    JF - Biology of Reproduction

    SN - 0006-3363

    IS - 2

    M1 - 55

    ER -