title: Serelaxin improves the pathophysiology of placental ischemia in the reduced uterine perfusion pressure rat model of preeclampsia.
abstract: Preeclampsia is a hypertensive disorder of pregnancy that has limited therapeutic options. In healthy pregnancy, relaxin plays an important vasodilatory role to maintain vascular compliance; however, currently, there is no preclinical evidence to support the use of relaxin during preeclampsia. Therefore, the goal of this study was to test the hypothesis that recombinant human relaxin-2 (Serelaxin, Novartis; RLX) could reduce mean arterial pressure (MAP) and improve uterine artery resistance index (UARI) and nitric oxide bioavailability, and/or decrease prepro-endothelin-1 (PPET-1), soluble fms-like tyrosine kinase-1 (sFlt-1), and TNF-α) in the reduced uterine perfusion pressure (RUPP) model of preeclampsia. On day 14 of gestation (GD14), pregnant rats were assigned to normal pregnant (NP), RUPP, RUPP+RLX, or NP+RLX groups. Treated rats received RLX at 0.4 μg/h or RLX2 4 μg/h RLX via minipump implanted on GD14. On GD18, carotid arterial catheters were inserted, and on GD19, MAP and tissues were collected. MAP was increased in RUPP rats compared with NP but was lowered with either dose of RLX. UARI and sFlt-1 were significantly improved in both treated RUPP groups. Total circulating nitrate-nitrite improved and placental PPET-1 and TNF-α were significantly decreased with the higher dose of RLX. Renal cortex PPET-1 was reduced with both doses of RLX. In conclusion, Serelaxin improved blood pressure, sFlt-1, TNF-α, UARI, and nitric oxide bioavailability and PPET-1 in a rat model of preeclampsia, thereby suggesting a potential therapeutic role for RLX in maintaining maternal health and prolonging pregnancy in the face of placental ischemia.
authors.affiliation: Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississippi; and.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Santiago-Font
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Lorena M
authors.initials: LM
authors.lastname: Amaral
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Jessica
authors.initials: J
authors.lastname: Faulkner
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Tarek
authors.initials: T
authors.lastname: Ibrahim
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Venkata Ramana
authors.initials: VR
authors.lastname: Vaka
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Cunningham
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi bblamarca@umc.edu.
authors.forename: Babbette
authors.initials: B
authors.lastname: LaMarca
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007511:Ischemia / Q000503:physiopathology / Q000517:prevention & control; D010920:Placenta / Q000098:blood supply* / Q000503:physiopathology; D011225:Pre-Eclampsia / Q000503:physiopathology* / Q000517:prevention & control*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D012065:Relaxin / Q000008:administration & dosage*; D055988:Uterine Artery / Q000187:drug effects / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D011994:Recombinant Proteins; C577649:serelaxin protein, human; D012065:Relaxin
keywords: dilation; hypertension; inflammation; pregnancy