Angiotensin AT1 receptor blockade fails to attenuate pressure-overload cardiac hypertrophy in fetal sheep. Am J Physiol 1997 Oct;273(4):R1501-8
Date
11/15/1997Pubmed ID
9362317DOI
10.1152/ajpregu.1997.273.4.R1501Scopus ID
2-s2.0-0030667188 (requires institutional sign-in at Scopus site) 38 CitationsAbstract
We examined the hypothesis that endogenous angiotensin II and angiotensin type 1 (AT1) receptors participate in the development of fetal right ventricular hypertrophy by studying the effects of AT1 receptor blockade on cardiac growth in fetal sheep subjected to constrictive banding of the pulmonary artery (PA). Seven pairs of twin fetuses were studied beginning at 126 +/- 1 days gestation (term = 145 days). One twin was given losartan (10 mg kg(-1) x day(-1) i.v.) for 7 consecutive days after PA banding, and the other twin served as a saline-treated, PA-banded control. Four additional pairs of twins served as sham-operated controls. Fetal heart rate (HR) and mean arterial blood pressure (MABP) were similar in the two groups of PA-banded animals before treatment and remained unchanged in the PA-banded control group. Losartan resulted in a significant decrease (P < 0.05) in MABP between days 0 and 7, whereas HR was not affected. Total body weight of the losartan-treated animals was significantly less (P < 0.05) than twin PA-banded controls and nonbanded fetuses. Right ventricle weight-to-body weight ratios were similar in saline (2.29 +/- 0.34 g/kg) and losartan-treated (2.11 +/- 0.15 g/kg) PA-banded animals and significantly greater than that in nonbanded fetuses (1.52 +/- 0.07 g/kg). Similar differences were seen in the right ventricle weight-to-left ventricle weight ratios. Right and left ventricle AT1 receptor mRNA and protein expression were also similar among the three groups, as were AT2 receptor mRNA levels. These data suggest that endogenous angiotensin II does not contribute to the development of pressure overload-induced right ventricular hypertrophy during fetal life and that expression of angiotensin receptors is not altered by increased afterload in the ovine fetus.
Author List
Segar JL, Scholz TD, Bedell KA, Smith OM, Huss DJ, Guillery ENAuthor
Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiotensin Receptor AntagonistsAnimals
Arteries
Blood
Body Weight
Cardiomegaly
Fetal Heart
Fetus
Hemodynamics
Hypertension
Ligation
Organ Size
Pulmonary Artery
RNA, Messenger
Receptors, Angiotensin
Sheep