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ANG II modulation of cardiac growth and remodeling in immature fetal sheep. Am J Physiol Regul Integr Comp Physiol 2015 Jun 01;308(11):R965-72

Date

03/27/2015

Pubmed ID

25810382

Pubmed Central ID

PMC4451391

DOI

10.1152/ajpregu.00034.2015

Scopus ID

2-s2.0-84930898311   5 Citations

Abstract

ANG II increases fetal blood pressure and stimulates fetal heart growth; however, little is known regarding its direct effects on cardiomyocytes in vivo. We sought to determine whether ANG II stimulates heart growth and cardiomyocyte hypertrophy and/or hyperplasia in utero in the immature fetal heart independent of the effects on cardiac afterload. In twin gestation, fetal sheep at ∼100 days gestation (term 145 days), one fetus received a chronic (6 days) infusion of ANG II alone (50 μg·kg(-1)·min(-1)) or ANG II plus nitroprusside (NTP) to attenuate the increase in blood pressure; noninstrumented twins served as controls. ANG II alone, but not ANG II + NTP resulted in a significant increase in heart mass (left and right ventricle + septum, corrected for body weight) compared with controls. ANG II, but not ANG II+NTP, also significantly increased cardiomyocyte area compared with control and increased the percentage of binucleated myocytes. ANG II with or without concomitant infusion of NTP increased cardiac PCNA expression, a marker of proliferation. Steady-state protein expression of terminal mitogen-activated protein kinases, cyclin B1, cyclin E1, and p21 were similar among groups. We conclude that in vivo, ANG II increases fetal cardiac mass via cardiomyocyte hypertrophy, differentiation, and to a lesser extent hyperplasia. The effects of ANG II on hypertrophy appear dependent upon the increase in blood pressure (mechanical load), whereas effects on proliferation are load-independent.

Author List

Sandgren J, Scholz TD, Segar JL

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Antihypertensive Agents
Biomarkers
Blood Pressure
Cardiomegaly
Cell Differentiation
Cell Enlargement
Cell Proliferation
Cell Size
Cyclin B1
Cyclin E
Cyclin-Dependent Kinase Inhibitor p21
Fetal Heart
Gestational Age
Hyperplasia
Hypertension
Mitogen-Activated Protein Kinases
Myocytes, Cardiac
Nitroprusside
Proliferating Cell Nuclear Antigen
Sheep
Signal Transduction
Time Factors
Vasodilator Agents
jenkins-FCD Prod-400 0f9a74600e4e79798f8fa6f545ea115f3dd948b2