title: Undernutrition in utero augments systolic blood pressure and cardiac remodeling in adult mouse offspring: possible involvement of local cardiac angiotensin system in developmental origins of cardiovascular disease.
abstract: Evidence has emerged that undernutrition in utero is a risk factor for cardiovascular disorders in adulthood, along with genetic and environmental factors. Recently, the local expression of angiotensinogen and related bioactive substances has been demonstrated to play a pivotal role in cardiac remodeling, i.e. fibrosis and hypertrophy. The aim of the present study was to clarify the possible involvement of the local cardiac angiotensin system in fetal undernutrition-induced cardiovascular disorders. We developed a mouse model of undernutrition in utero by maternal food restriction, in which offspring (UN offspring) showed an increase in systolic blood pressure (8 wk of age, P < 0.05; and 16 wk, P < 0.01), perivascular fibrosis of the coronary artery (16 wk, P < 0.05) and cardiac cardiomegaly (16 wk, P < 0.01), and cardiomyocyte enlargement, concomitant with a significant augmentation of angiotensinogen (P < 0.05) and endothelin-1 (P < 0.01) mRNA expression and a tendency to increase in immunostaining for both angiotensin II and endothelin-1 in the left ventricles (16 wk). These findings suggest that fetal undernutrition activated the local cardiac angiotensin system-associated bioactive substances, which contributed, at least partly, to the development of cardiac remodeling in later life, in concert with the effects of increase in blood pressure.
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawamura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itoh
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yura
authors.forename: Haruta
authors.initials: H
authors.lastname: Mogami
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Suga
authors.forename: Hisashi
authors.initials: H
authors.lastname: Makino
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Yasunao
authors.initials: Y
authors.lastname: Yoshimasa
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sagawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Fujii
mesh_terms: D000804:Angiotensin II / Q000097:blood / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000196:embryology / Q000209:etiology*; D005260:Female; D048070:Fetal Nutrition Disorders / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology; D044342:Malnutrition / Q000097:blood / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000097:blood; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000503:physiopathology*; D012084:Renin-Angiotensin System; D012970:Sodium Glutamate / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D020738:Leptin; D000804:Angiotensin II; D009569:Nitric Oxide; D012970:Sodium Glutamate