title: Angiotensin II receptor antagonist reduces subsequent uterine arterial dysfunction in pregnant offspring of protein-restricted rat dams.
abstract: OBJECTIVE
  A low-protein diet (LPD) during pregnancy induces vascular dysfunction and hypertension in the offspring, prevented by administration of an angiotensin II type 1 (AT(1)) receptor antagonist in early life to the offspring. Whether such protection extends to subsequent pregnancy is unknown; we therefore hypothesized that administration of a specific AT(1) receptor antagonist (losartan) in early life to offspring of LPD dams would improve vascular dysfunction in their uterine arteries when they, in turn, were pregnant.
  
  
  METHODS
  Pregnant rats were randomly divided into two dietary groups fed a control (C) or protein-restricted (R) diet throughout pregnancy. Between two and 10 weeks postnatally, female offspring (F(1)) were randomly assigned to drink either pure tap water (CO, RO) or water with losartan (CL, RL). Offspring were mated and killed on gestational day 19 or 20 in order to investigate uterine artery function.
  
  
  RESULTS
  In pregnant offspring, vasoconstriction of the uterine arteries to phenylephrine (PE) and the thromboxane A2 mimetic U46619 was greater in RO than CO (F(1)). Responses to both antagonists were suppressed in RL (F(1)). Relaxation to sodium nitroprusside was increased in RO versus CO and suppressed in RL versus RO (F(1)).
  
  
  CONCLUSIONS
  Administration of an AT(1) receptor antagonist to offspring during the suckling and juvenile period improves the uterine vascular dysfunction in pregnancy induced by prior maternal LPD during their development. Such treatment may contribute to decreasing the transmitted risks of maternal malnutrition from offspring to the subsequent generation.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Juntendo University, Tokyo, Japan. tsaito2008@hotmail.co.jp
authors.forename: Tomomi
authors.initials: T
authors.lastname: Saito
authors.forename: Yuka
authors.initials: Y
authors.lastname: Musha
authors.forename: Miho
authors.initials: M
authors.lastname: Miyakawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Itoh
authors.forename: Mareki
authors.initials: M
authors.lastname: Ohtsuji
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hanson
authors.forename: Satoru
authors.initials: S
authors.lastname: Takeda
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D009599:Nitroprusside / Q000494:pharmacology; D016491:Peripheral Vascular Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D055988:Uterine Artery / Q000187:drug effects* / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019808:Losartan