Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Angiotensin II in cardiac pressure-overload hypertrophy in fetal sheep. Am J Physiol Regul Integr Comp Physiol 2001 Dec;281(6):R2037-47

Date

11/14/2001

Pubmed ID

11705791

DOI

10.1152/ajpregu.2001.281.6.R2037

Scopus ID

2-s2.0-0035658522   27 Citations

Abstract

We previously demonstrated in fetal sheep that blockade of ANG II type 1 (AT(1)) receptors did not attenuate an increase in right ventricle (RV) mass resulting from partial occlusion of the pulmonary artery (PA). We have now determined the effects of AT(2)-receptor blockade (PD-123319, 10 mg. kg(-1). day(-1) continuous iv) on the response of the fetal RV to PA banding for 7 days. Four groups of fetuses (each n = 7) were studied beginning at 126 +/- 1 days gestation (term 145 days). RV weight-to-body weight ratio (RV wt/body wt) increased (P < 0.05) in PA-banded (6.00 +/- 0.09 g/kg) and PA-banded + PD-123319 (6.19 +/- 0.27 g/kg) compared with control (5.17 +/- 0.17 g/kg) and PD-123319-infused (5.27 +/- 0.35 g/kg) fetuses (means +/- SE). Blood pressure and heart rate were similar in all groups. PD-123319 produced a decrease (P < 0.05) in AT(1) but not AT(2) mRNA levels in both fetal ventricles. To examine the effect of ANG II on fetal heart growth, twin fetal sheep were infused with either ANG II (twin received vehicle) or phenylephrine (Phe) (twin received vehicle) continuously for 7 days. Mean arterial blood pressure was 20-25 mmHg higher in ANG II and Phe fetuses compared with controls. The rate-pressure product was similar in ANG II and Phe fetuses and 40-50% greater than controls. Phe resulted in no change in RV wt/body wt or left ventricle-to-body weight ratio (LV wt/body wt) compared with controls. In contrast, ANG II produced a selective increase (27 +/- 5%, P < 0.05) in LV wt/body wt; no effect was seen on the RV. ANG II produced a decrease (P < 0.05) in LV but not RV AT(1) mRNA levels compared with controls; no effect was seen with Phe. The data demonstrate that in the ovine fetus, AT(2) receptors do not contribute to the maintenance of blood pressure or the development of pressure-overload RV hypertrophy. Elevated ANG II levels produce a selective increase in LV mass in the fetal sheep that is, in part, independent of increased systolic load.

Author List

Segar JL, Dalshaug GB, Bedell KA, Smith OM, Scholz TD

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

Adrenal Glands
Angiotensin II
Angiotensin Receptor Antagonists
Animals
Blood Pressure
Brain
Cardiomegaly
Female
Gestational Age
Heart
Imidazoles
Kidney
Lung
Organ Size
Phenylephrine
Pregnancy
Pulmonary Artery
Pyridines
Receptor, Angiotensin, Type 2
Sheep
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0