Current Hypertension Reports

, Volume 13, Issue 6, pp 409–420 | Cite as

Effects of Relaxin on Arterial Dilation, Remodeling, and Mechanical Properties

  • Kirk P. Conrad
  • Sanjeev G. Shroff
Mediators, Mechanisms, and Pathways in Tissue Injury (Heinrich Taegtmeyer and Steven Atlas, Section Editors)


Administering relaxin to conscious rats and humans elicits systemic and renal vasodilation. The molecular mechanisms vary according to the duration of relaxin exposure—so-called “rapid” (within minutes) or “sustained” (hours to days) vasodilatory responses—both being endothelium-dependent. Rapid responses are mediated by Gαi/o protein coupling to phosphoinositol-3 kinase/Akt (protein kinase B)–dependent phosphorylation and activation of nitric oxide synthase. Sustained responses are mediated by vascular endothelial and placental growth factors, as well as increases in arterial gelatinase activity. Thus, after hours or days of relaxin treatment, respectively, arterial MMP-9 or MMP-2 hydrolyze “big” endothelin (ET) at a gly-leu bond to form ET1-32, which in turn activates the endothelial ETB receptor/nitric oxide vasodilatory pathway. Administration of relaxin to conscious rats also increases global systemic arterial compliance and passive compliance of select isolated blood vessels such as small renal arteries (SRA). The increase in SRA passive compliance is mediated by both geometric remodeling (outward) and compositional remodeling (decreased collagen). Relaxin-induced geometric remodeling has also been observed in brain parenchymal arteries, and this remodeling appears to be via the activation of peroxisome proliferator–activated receptor-γ. Given the vasodilatory and arterial remodeling properties of relaxin, the hormone may have therapeutic potential in the settings of abnormal pregnancies, heart failure, and pathologies associated with stiffening of arteries.


Relaxin Hypertension Pregnancy Preeclampsia Heart failure Systemic hemodynamics Arterial compliance Renal circulation Artery Angiogenic growth factors Matrix metalloproteinase Endothelin Nitric oxide Osmoregulation Collagen Elastin Endothelium Smooth muscle Arterial remodeling 



The work in the authors’ laboratory would not have been possible without the invaluable contributions of many outstanding colleagues and trainees over the years, particularly Lee A. Danielson, PhD; Laura J. Parry, PhD; Jacqueline Novak, PhD; Arun Jeyabalan, MD; John M. Davison, MD; Jonathan T. McGuane, PhD (Postdoctoral Fellow); and Dan O. Debrah (Predoctoral Fellow). We gratefully acknowledge the financial support of the National Institutes of Health (K11 HD00662, RO1 HD030325, RO1 DK063321, RO1 HL067937, and R21 HL093334), the 8th Mallinckrodt Scholar Award, New Mexico Heart Association Flinn Newly Independent Investigator Award, a Grant-in-Aid from the American Heart Association (No. 0855090E), and the McGinnis Endowed Chair Funds.


Conflicts of Interest: K. Conrad: Honoraria for consulting on relaxin with the pharmaceutical industry and patents related to relaxin; S. Shroff: patents related to relaxin.


Papers of particular interest, published recently, have been highlighted as: • Of importance

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Departments of Physiology and Functional Genomics, and of Obstetrics and Gynecology, and the D.H. Barron Reproductive and Perinatal Biology Research ProgramUniversity of FloridaGainesvilleUSA
  2. 2.Departments of Bioengineering and MedicineUniversity of PittsburghPittsburghUSA

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