Relaxin deficiency attenuates pregnancy-induced adaptation of the mesenteric artery to angiotensin II in mice

Sarah A. Marshall, Chen Huei Leo, Sevvandi N. Senadheera, Jane E. Girling, Marianne Tare, Laura J. Parry

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25 Citations (Scopus)

Abstract

Pregnancy is associated with reduced peripheral vascular resistance, underpinned by changes in endothelial and smooth muscle function. Failure of the maternal vasculature to adapt correctly leads to serious pregnancy complications, such as preeclampsia. The peptide hormone relaxin regulates the maternal renal vasculature during pregnancy; however, little is known about its effects in other vascular beds. This study tested the hypothesis that functional adaptation of the mesenteric and uterine arteries during pregnancy will be compromised in relaxin-deficient (Rln−/−) mice. Smooth muscle and endothelial reactivity were examined in small mesenteric and uterine arteries of nonpregnant (estrus) and late-pregnant (day 17.5) wild-type (Rln+/+) and Rln−/− mice using wire myography. Pregnancy per se was associated with significant reductions in contraction to phenylephrine, endothelin-1, and ANG II in small mesenteric arteries, while sensitivity to endothelin-1 was reduced in uterine arteries of Rln+/+ mice. The normal pregnancy-associated attenuation of ANG II-mediated vasoconstriction in mesenteric arteries did not occur in Rln−/− mice. This adaptive failure was endothelium-independent and did not result from altered expression of ANG II receptors or regulator of G protein signaling 5 (Rgs5) or increases in reactive oxygen species generation. Inhibition of nitric oxide synthase with L-NAME enhanced ANG II-mediated contraction in mesenteric arteries of both genotypes, whereas blockade of prostanoid production with indomethacin only increased ANG II-induced contraction in arteries of pregnant Rln+/+ mice. In conclusion, relaxin deficiency prevents the normal pregnancy-induced attenuation of ANG II-mediated vasoconstriction in small mesenteric arteries. This is associated with reduced smooth muscle-derived vasodilator prostanoids.
Original languageEnglish
Pages (from-to)R847-R857
Number of pages11
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume310
Issue number9
DOIs
Publication statusPublished - 1 May 2016

Keywords

  • angiotensin
  • pregnancy
  • relaxin
  • vascular

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