Oral Presentation 6th Australian Health and Medical Research Congress 2012

Regulation of the maternal vascular adaptations to pregnancy (#240)

Laura J Parry 1 , Jonathan H Gooi 1 , Lenka A Vodstcil 1 2 , Maria Jelinic 1 , Meghan Richardson 1 , Kelly O'Sullivan 1 , Mary E Wldoek 1 , Kirk P Conrad 3 , Marianne Tare 4
  1. Department of Zoology, University of Melbourne, Melbourne, VIC, Australia
  2. Department of Physiology, University of Melbourne, Melbourne, VIC, Australia
  3. Department of Physiology and Functional Genomics, University of Florida, Florida, USA
  4. Department of Physiology, , Monash University, Melbourne, VIC, Australia

Pregnancy is a unique physiological condition, with profound renal and systemic vasodilation epitomizing the maternal cardiovascular adaptations. In addition, the uteroplacental vasculature undergoes dramatic structural and functional modifications to allow for a largeincrease in blood flow to the feto-placental unit. These vascular adaptations are achieved through a number of mechanisms including structural changes in the artery wall and changes in endothelial and smooth muscle reactivity. Several endothelium-derived vasodilators (nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor) are also known to be up-regulated during pregnancy and contribute to these important vascular adaptations. Failure of the maternal vascular system to adapt to pregnancy, with reduced placental perfusion in early gestation, gives rise to serious complications including preeclampsia and intrauterine growth restriction.

Our research has identified the peptide hormone relaxin as a mediator of both renal and systemic hemodynamic adaptations to pregnancy. We recently demonstrated relaxin receptors in endothelial and vascular smooth muscle cells in arteries and veins. Relaxin treatment in rats and mice stimulates endothelium-dependent vasodilation in small renal, mesenteric and uterine arteries. This is mediated through vascular endothelial and placental growth factors, increases in arterial gelatinase activity and activation of the endothelin B receptor/nitric oxide vasodilatory pathway. Relaxin also increases arterial compliance and outward hypertrophic remodelling. Neutralization of circulating relaxin in late pregnant rats with a monoclonal antibody prevents the reduction in myogenic reactivity seen in control pregnant rats, and increases uterine artery wall stiffness. Similar effects are observed in relaxin gene knockout mice. Furthermore, there is evidence of proteinuria and decreased fetal weight in these “vascular compromised” relaxin-deficient mice. Our data demonstrate the important vascular actions of relaxin in pregnancy and illustrate that a lack of relaxin can disrupt maternal vascular adaptations to pregnancy and adversely affect maternal health.