title: Effects of relaxin on arterial dilation, remodeling, and mechanical properties.
abstract: 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 G(αi/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 ET(1-32), which in turn activates the endothelial ET(B) 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.
authors.affiliation: Department of Physiology and Functional Genomics, D.H. Barron Reproductive and Perinatal Biology Research Program, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA. kpconrad@ufl.edu
authors.forename: Kirk P
authors.initials: KP
authors.lastname: Conrad
authors.forename: Sanjeev G
authors.initials: SG
authors.lastname: Shroff
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects*; D001696:Biomechanical Phenomena / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006333:Heart Failure; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology*; D011225:Pre-Eclampsia / Q000473:pathology; D011247:Pregnancy; D012065:Relaxin / Q000494:pharmacology*; D027724:Reproductive Techniques, Assisted; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D012065:Relaxin