Cardiac Hypertrophy Is Not Attenuated by Angiotensin Type 2 (AT2) Receptor Blockade in Fetal Sheep • 139

Abstract

We have previously shown in pulmonary artery (PA) banded fetal sheep that angiotensin II type 1 (AT1) receptor blockade fails to attenuate the development of right ventricular hypertrophy (RVH) and does not alter expression of cardiac AT1 or AT2 mRNA (Am J Physiol 42:R1501-8, 1997). Because AT2 mRNA is expressed in higher abundance in fetal compared to neonatal heart, and because there is evidence suggesting these receptors are involved in cellular growth and differentiation, we tested the hypothesis that endogenous angiotensin II and AT2 receptors participate in the development of fetal RVH. Three groups of fetuses were studied beginning at 126 d gestation(term 145 d) and were given either the AT2 receptor antagonist PD 123319 (5 mg/kg/d iv) for 7 consecutive days (n=5), PA banding plus PD 123319 (n=5), or sham surgery alone (n=4). Fetal heart rate and arterial pressure were similar among groups before and after the treatment period. Body weight and left ventricle weight/body weight at the end of study were also similar among groups. However, RV weight/body weight was significantly greater (p<0.05) in PA banded animals (2.38±.07 g/kg) than in PD alone (1.83±.14 g/kg) or sham fetuses (1.72±.07). Northern blot analysis revealed that PD alone decreased cardiac AT1 mRNA levels (55±7% and 73±13% of control (100%) in RV and LV, respectively). Similar decreases were seen in the RV (76±16%) and LV (71±9%) of PA banded animals. No changes in cardiac AT2 mRNA levels were detected in any group. These data suggest that in the ovine fetus, AT2 receptors do not contribute to the maintenance of blood pressure or the development of pressure-overload RV hypertrophy. In addition, expression of cardiac AT1 but not AT2 mRNA is altered by AT2 receptor blockade.