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

• Published in: Endocrinology (Philadelphia) 2007-03, Vol.148 (3), p.1218-1225
• Main Authors: Kawamura, Makoto, Itoh, Hiroaki, Yura, Shigeo, Mogami, Haruta, Suga, Shin-Ichi, Makino, Hisashi, Miyamoto, Yoshihiro, Yoshimasa, Yasunao, Sagawa, Norimasa, Fujii, Shingo
• Format: Article
• Language: English
• Subjects: Angiotensin; Angiotensin II; Angiotensin II - blood; Angiotensin II - metabolism; Angiotensin II - physiology; Angiotensinogen; Animals; Biological activity; Biological and medical sciences; Blood Pressure; Cardiomyocytes; Cardiovascular diseases; Cardiovascular Diseases - embryology; Cardiovascular Diseases - etiology; Coronary artery disease; Disorders; Endothelin 1; Environmental factors; Female; Fetal Nutrition Disorders - blood; Fetal Nutrition Disorders - etiology; Fetal Nutrition Disorders - physiopathology; Fetuses; Fibrosis; Food availability; Fundamental and applied biological sciences. Psychology; Gene expression; Heart Ventricles - metabolism; Hypertrophy; Leptin - pharmacology; Malnutrition; Malnutrition - blood; Malnutrition - complications; Medical sciences; Metabolic diseases; Mice; Mice, Inbred C57BL; Nitric Oxide - blood; Offspring; Other nutritional diseases (malnutrition, nutritional and vitamin deficiencies...); Pregnancy; Prenatal Exposure Delayed Effects - blood; Prenatal Exposure Delayed Effects - physiopathology; Pressure effects; Renin-Angiotensin System; Risk factors; Sodium Glutamate - pharmacology; Undernutrition; Ventricular Remodeling - drug effects; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2006-0706

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.