Maternal food restriction modulates cerebrovascular structure and contractility in adult rat offspring: effects of metyrapone

Am J Physiol Regul Integr Comp Physiol. 2014 Mar 15;306(6):R401-10. doi: 10.1152/ajpregu.00436.2013. Epub 2014 Jan 29.


Although the effects of prenatal undernutrition on adult cardiovascular health have been well studied, its effects on the cerebrovascular structure and function remain unknown. We used a pair-fed rat model of 50% caloric restriction from day 11 of gestation to term, with ad libitum feeding after birth. We validated that maternal food restriction (MFR) stress is mediated by glucocorticoids by administering metyrapone, a corticosterone synthesis inhibitor, to MFR mothers at day 11 of gestation. At age 8 mo, offspring from Control, MFR, and MFR + Metyrapone groups were killed, and middle cerebral artery (MCA) segments were studied using vessel-bath myography and confocal microscopy. Colocalization of smooth muscle α-actin (SMαA) with nonmuscle (NM), SM1 and SM2 myosin heavy-chain (MHC) isoforms was used to assess smooth muscle phenotype. Our results indicate that artery stiffness and wall thickness were increased, pressure-evoked myogenic reactivity was depressed, and myofilament Ca(2+) sensitivity was decreased in offspring of MFR compared with Control rats. MCA from MFR offspring exhibited a significantly greater SMαA/NM colocalization, suggesting that the smooth muscle cells had been altered toward a noncontractile phenotype. MET significantly reversed the effects of MFR on stiffness but not myogenic reactivity, lowered SMαA/NM colocalization, and increased SMαA/SM2 colocalization. Together, our data suggest that MFR alters cerebrovascular contractility via both glucocorticoid-dependent and glucocorticoid-independent mechanisms.

Keywords: cerebral arteries; glucocorticoids; myogenic reactivity; myosin heavy-chain isoforms; smooth muscle phenotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Calcium / metabolism
  • Caloric Restriction*
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / physiopathology
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology*
  • Corticosterone / metabolism
  • Enzyme Inhibitors / pharmacology
  • Female
  • Male
  • Malnutrition / physiopathology*
  • Metyrapone / pharmacology*
  • Middle Cerebral Artery / abnormalities
  • Middle Cerebral Artery / drug effects
  • Middle Cerebral Artery / physiology
  • Muscle, Smooth, Vascular / abnormalities
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / pathology
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology


  • Enzyme Inhibitors
  • Calcium
  • Corticosterone
  • Metyrapone