Pregnancy is a unique physiological condition, with profound maternal renal and systemic vascular adaptations. These are achieved through a number of mechanisms including changes in vascular reactivity to vasoconstrictors and vasodilators. Endothelium-derived mediators of vasodilation, nitric oxide (NO), prostacyclin, endothelium-derived hyperpolarization are also upregulated during pregnancy and contribute to these important vascular adaptations. Endothelial dysfunction in the systemic vasculature is a hallmark of preeclampsia (PE), and is characterized by impaired vascular reactivity resulting from reduced NO availability, increased sensitivity to vasoconstrictors and elevated vascular oxidative stress. Therefore, our research group has explored the possibility of developing treatments to alleviate symptoms of PE by improving vascular function in maternal systemic arteries. We have focused on the peptide hormone relaxin, which mediates maternal haemodynamic adaptations to pregnancy.
Clinical hemodynamic studies show that a short-term relaxin infusion results in a rapid decrease in systemic vascular resistance, which is sustained for a prolonged period of time. This implies that relaxin has long-lasting vasodilator effects on blood vessels. Relaxin treatment (5 days) in rats stimulates endothelium-dependent vasodilation in small resistance arteries; this is mediated through vascular endothelial and placental growth factors, increases in arterial gelatinase activity and activation of the NO vasodilatory pathway. We recently discovered that a single bolus i.v. injection of relaxin enhances bradykinin-mediated endothelium-dependent relaxation, an effect that is associated with vasodilator prostanoids and sustained for >24 hours after administration in the absence of circulating relaxin. In addition to its vasorelaxation effects, relaxin reduces the contraction response to endothelin-1 and attenuates the stimulated production of superoxide and nitrotyrosine in “damaged” rat aortic rings incubated with TNF-alpha. Taken together, these findings suggest that relaxin has the potential to rapidly alleviate endothelial dysfunction and induce long-term beneficial effects on the vascular system in women diagnosed with PE.