title: Effect of maternal nutrient restriction and melatonin supplementation from mid to late gestation on vascular reactivity of maternal and fetal placental arteries.
abstract: BACKGROUND
  Maternal nutrient restriction and decreased scotophase concentrations of melatonin have been associated with severely compromised pregnancies. We hypothesized that melatonin supplementation in a compromised pregnancy enhances the bradykinin (BK)-induced relaxations of placental arteries thereby ensuring sufficient umbilical blood flow to the developing fetus.
  
  
  METHODS
  Pregnant ewes (n = 31) were fed an adequate (ADQ) or nutrient restricted (RES) diet supplemented with 5 mg of melatonin (MEL) or without melatonin (CON) from day 50 to 130 of gestation. On day 130 of gestation, the maternal (caruncular; CAR) and fetal (cotyledonary; COT) placental arteries were suspended in organ chambers for isometric tension recording.
  
  
  RESULTS
  There were no treatment or dietary effects on CAR arteries for any vasoactive agent. However, in COT arteries, MEL ewes were more sensitive (P < 0.01) to bradykinin-induced relaxation than CON ewes. There was a melatonin by nutritional level interaction (P < 0.01) with sodium nitroprusside-induced relaxation of COT arteries where CON-RES were more sensitive to sodium nitroprusside compared to CON-ADQ, which was in contrast to when ewes were fed MEL. There was a significant melatonin by nutritional interaction (P = 0.04) for responsiveness to norepinephrine. The sensitivity of the COT arteries to norepinephrine in CON-RES ewes was decreased compared to CON-ADQ. Melatonin supplementation, regardless of maternal dietary intake, resulted in COT arteries having similar responsiveness to CON-RES ewes.
  
  
  CONCLUSIONS
  An increase in placental vessel sensitivity to bradykinin-induced relaxation may contribute to melatonin-induced increases in umbilical artery blood flow.
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, USA.
authors.forename: P
authors.initials: P
authors.lastname: Shukla
authors.affiliation: Department of Animal Sciences, North Dakota State University, Fargo, ND 58108-6050, USA.
authors.forename: C O
authors.initials: CO
authors.lastname: Lemley
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, USA.
authors.forename: N
authors.initials: N
authors.lastname: Dubey
authors.affiliation: Department of Animal Sciences, North Dakota State University, Fargo, ND 58108-6050, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Meyer
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: O'Rourke
authors.affiliation: Department of Animal Sciences, North Dakota State University, Fargo, ND 58108-6050, USA. Electronic address: Kim.Vonnahme@ndsu.edu.
authors.forename: K A
authors.initials: KA
authors.lastname: Vonnahme
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D004032:Diet; D005260:Female; D039382:Maternal Nutritional Physiological Phenomena; D008550:Melatonin / Q000008:administration & dosage* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply / Q000187:drug effects; D021041:Placental Circulation / Q000187:drug effects*; D011247:Pregnancy; D034561:Sheep, Domestic; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D000804:Angiotensin II; D008550:Melatonin; D001920:Bradykinin; D009638:Norepinephrine
keywords: Arterial relaxation; Gestation; Melatonin; Nutrient restriction; Placental blood flow; Sheep