Pregnancy is associated with a reduction in peripheral vascular resistance, underpinned by structural remodelling and altered reactivity of the endothelium and smooth muscle. The peptide hormone relaxin plays a major role in regulating the maternal renal vasculature during pregnancy. We have also demonstrated that relaxin deficiency in rats and mice results in increased uterine artery stiffness in late pregnancy, affecting uterine blood flow. Little is known about the actions of relaxin on vascular reactivity. Therefore, this study tested the hypothesis that vascular reactivity will be altered in the uterine and mesenteric arteries of pregnant relaxin knock-out (Rln-/-) mice.
In late-pregnant (day 17.5) mice, myogenic reactivity was assessed in uterine arteries using pressure myography. Endothelial and smooth muscle reactivity was examined in small mesenteric arteries using wire myography. Myogenic reactivity was enhanced in uterine arteries from pregnant Rln-/- mice compared to age-matched wild-type (Rln+/+) animals. To examine the role of endothelium-derived vasodilators nitric oxide (NO) and prostanoids in the regulation of myogenic reactivity, the NO synthase inhibitor, L-NAME (200 µmol/L) and cyclooxygenase inhibitor, indomethacin (1 µmol/L) were used. Treatment with L-NAME and indomethacin further enhanced myogenic reactivity in uterine arteries from both groups. In mesenteric arteries the sensitivity to vasoconstrictors, angiotensin-II and phenylephrine were enhanced in pregnant Rln-/- mice, with no change in response to the thromboxane A2 analogue U-46619 and endothelin-1. Responses to the endothelial agonists, acetylcholine and Bradykinin, were unaltered between the two groups.
In summary, our data show that myogenic reactivity and sensitivity to vasoconstrictors are enhanced in the vasculature of late-pregnant Rln-/- mice. Thus, relaxin deficiency results in an increase in peripheral vascular resistance, which may contribute to vascular complications of pregnancy including hypertension and intrauterine growth restriction.