Adrenomedullin relaxes rat uterine artery: Mechanisms and influence of pregnancy and estradiol

Gracious R. Ross, Uma Yallampalli, Pandu R R Gangula, Luckey Reed, K. Sathishkumar, Haijun Gao, Madhu Chauhan, Chandra Yallampalli

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    Uterine arteries play a major role in regulating uteroplacental blood flow. Failure to maintain blood flow to the uteroplacental compartment during pregnancy often results in intrauterine growth retardation. Immunohistochemical staining of adrenomedullin (AM), an endogenous vasoactive peptide, in uterine artery was intense in pregnant compared to nonpregnant rats, but it is not known whether AM directly relaxes uterine artery or not. In this study, we elucidated the mechanisms of uterine artery relaxation by AM and its regulation by pregnancy and female sex steroids. AM was able to relax uterine artery, and this relaxation was influenced positively by pregnancy and estradiol as evidenced by the increased pD2 and Emax values of AM. Both pregnancy and estradiol treatment to ovariectomized rats amplified RAMP3 expression in uterine arteries while progesterone had no effect. AM-induced uterine artery relaxation is predominantly endothelium-dependent. The AM receptor antagonist CGRP8-37 is more potent than AM22-52 in inhibiting the AM relaxation, indicating the involvement of AM2 receptor subtype. Moreover, AM uses the classical nitric oxide-cyclic guanosine monophosphate pathway along with KCa channels to mediate the vasodilatory effect in uterine artery. In conclusion, sensitivity of uterine artery to AM-induced relaxation is increased with pregnancy or estradiol treatment by increasing RAMP3 expression, suggesting an important role for AM in regulating the uterine hemodynamics, probably maintaining uterine blood flow during pregnancy and in pre- and postmenopausal cardiovascular adaptation differences.

    Original languageEnglish (US)
    Pages (from-to)4485-4493
    Number of pages9
    JournalEndocrinology
    Volume151
    Issue number9
    DOIs
    StatePublished - 2010

    Fingerprint

    Adrenomedullin
    Uterine Artery
    Estradiol
    Pregnancy
    Adrenomedullin Receptors
    Fetal Growth Retardation
    Cyclic GMP
    Endothelium
    Progesterone
    Nitric Oxide
    Hemodynamics
    Steroids
    Staining and Labeling

    ASJC Scopus subject areas

    • Endocrinology
    • Medicine(all)

    Cite this

    Ross, G. R., Yallampalli, U., Gangula, P. R. R., Reed, L., Sathishkumar, K., Gao, H., ... Yallampalli, C. (2010). Adrenomedullin relaxes rat uterine artery: Mechanisms and influence of pregnancy and estradiol. Endocrinology, 151(9), 4485-4493. https://doi.org/10.1210/en.2010-0096

    Adrenomedullin relaxes rat uterine artery : Mechanisms and influence of pregnancy and estradiol. / Ross, Gracious R.; Yallampalli, Uma; Gangula, Pandu R R; Reed, Luckey; Sathishkumar, K.; Gao, Haijun; Chauhan, Madhu; Yallampalli, Chandra.

    In: Endocrinology, Vol. 151, No. 9, 2010, p. 4485-4493.

    Research output: Contribution to journalArticle

    Ross, GR, Yallampalli, U, Gangula, PRR, Reed, L, Sathishkumar, K, Gao, H, Chauhan, M & Yallampalli, C 2010, 'Adrenomedullin relaxes rat uterine artery: Mechanisms and influence of pregnancy and estradiol', Endocrinology, vol. 151, no. 9, pp. 4485-4493. https://doi.org/10.1210/en.2010-0096
    Ross GR, Yallampalli U, Gangula PRR, Reed L, Sathishkumar K, Gao H et al. Adrenomedullin relaxes rat uterine artery: Mechanisms and influence of pregnancy and estradiol. Endocrinology. 2010;151(9):4485-4493. https://doi.org/10.1210/en.2010-0096
    Ross, Gracious R. ; Yallampalli, Uma ; Gangula, Pandu R R ; Reed, Luckey ; Sathishkumar, K. ; Gao, Haijun ; Chauhan, Madhu ; Yallampalli, Chandra. / Adrenomedullin relaxes rat uterine artery : Mechanisms and influence of pregnancy and estradiol. In: Endocrinology. 2010 ; Vol. 151, No. 9. pp. 4485-4493.
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