Enhanced growth and improved vascular function in offspring from successive pregnancies in endothelial nitric oxide synthase knockout mice

Monica Longo, Venu Jain, Josje Langenveld, Yuri P. Vedernikov, Robert E. Garfield, Gary Hankins, Garland D. Anderson, George Saade

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Transgenic mice that lack endothelial nitric oxide synthase have offspring with growth deficiency and abnormal vascular reactivity in later life. Our objective was to evaluate the role of parity in the modulation of the fetal programming of growth and vascular responses in these transgenic mice. Oligoparous (0-2 previous pregnancies) and multiparous (5-9 previous pregnancies) nitric oxide synthase knockout (-/-KO) female mice were bred with nitric oxide synthase -/-KO and wild type (+/+WT) male mice to produce nitric oxide synthase -/-KO and maternally derived heterozygous (+/-Mat) litters. The pups were weighed weekly. Carotid arteries of the adult females from these litters were used for in vitro vascular reactivity studies. Nitric oxide synthase knockout and nitric oxide synthase maternal litters that were born to oligoparous mothers had significant growth lag compared with corresponding multiparous litters. Length-tension characteristics were not different between the groups. However, optimal diameter, which is a measure of vascular tensile properties and resistance, was decreased in oligoparous compared with multiparous female offspring. Acetylcholine-mediated vasorelaxation was abolished, and contraction by phenylephrine and Ca ++ was increased in oligoparous, but not multiparous, female offspring (P <. 05). These data support the role of abnormal uterine environment in the fetal programming of postnatal growth and vascular function in later life. Successive pregnancies may lead to maternal uterine adaptations that bypass the lack of a functional nitric oxide synthase, which leads to improvement in postnatal growth and vascular function in the offspring. Given the reported effect of parity on the risk of preeclampsia, similar mechanisms may be operative in human pregnancy.

Original languageEnglish (US)
Pages (from-to)1470-1476
Number of pages7
JournalAmerican Journal of Obstetrics and Gynecology
Volume191
Issue number4
DOIs
StatePublished - Oct 2004

Fingerprint

Nitric Oxide Synthase Type III
Knockout Mice
Nitric Oxide Synthase
Blood Vessels
Pregnancy
Growth
Fetal Development
Parity
Transgenic Mice
Mothers
Phenylephrine
Pre-Eclampsia
Carotid Arteries
Vasodilation
Acetylcholine

Keywords

  • Fetal programming
  • Mice
  • Parity
  • Preeclampsia
  • Uteroplacental perfusion

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

Enhanced growth and improved vascular function in offspring from successive pregnancies in endothelial nitric oxide synthase knockout mice. / Longo, Monica; Jain, Venu; Langenveld, Josje; Vedernikov, Yuri P.; Garfield, Robert E.; Hankins, Gary; Anderson, Garland D.; Saade, George.

In: American Journal of Obstetrics and Gynecology, Vol. 191, No. 4, 10.2004, p. 1470-1476.

Research output: Contribution to journalArticle

Longo, Monica ; Jain, Venu ; Langenveld, Josje ; Vedernikov, Yuri P. ; Garfield, Robert E. ; Hankins, Gary ; Anderson, Garland D. ; Saade, George. / Enhanced growth and improved vascular function in offspring from successive pregnancies in endothelial nitric oxide synthase knockout mice. In: American Journal of Obstetrics and Gynecology. 2004 ; Vol. 191, No. 4. pp. 1470-1476.
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