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.
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.
Kawamura
Makoto
M
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Itoh
Hiroaki
H
Yura
Shigeo
S
Mogami
Haruta
H
Suga
Shin-Ichi
S
Makino
Hisashi
H
Miyamoto
Yoshihiro
Y
Yoshimasa
Yasunao
Y
Sagawa
Norimasa
N
Fujii
Shingo
S
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
D020738:Leptin; D000804:Angiotensin II; D009569:Nitric Oxide; D012970:Sodium Glutamate