Maternal food restriction modulates cerebrovascular structure and contractility in adult rat offspring: effects of metyrapone.
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.
Center for Perinatal Biology, Divisions of Physiology and Pharmacology, School of Medicine, Loma Linda University, Loma Linda, California; and.
Lara M
LM
Durrant
Omid
O
Khorram
John N
JN
Buchholz
William J
WJ
Pearce
D000367:Age Factors; D000818:Animals; D002118:Calcium / Q000378:metabolism; D031204:Caloric Restriction; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D044342:Malnutrition / Q000503:physiopathology*; D008797:Metyrapone / Q000494:pharmacology*; D020768:Middle Cerebral Artery / Q000002:abnormalities / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000002:abnormalities / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D002118:Calcium; D003345:Corticosterone; D008797:Metyrapone
cerebral arteries; glucocorticoids; myogenic reactivity; myosin heavy-chain isoforms; smooth muscle phenotype