Characterization and Distribution of Angiotensin-II Receptors in the Primate Fetus

The binding characteristics and distribution of angiotensin-II (AII) receptors were studied in Cynomolgus monkey fetuses and one second trimester human fetus. In contrast to the adult monkey, in which binding was confined to the adrenal gland, kidney, and smooth muscle, autoradiographic studies in the monkey fetus revealed the presence of high density binding in mesenchymal tissue throughout the body, especially in skeletal muscle and dermis. In the kidney at 11 weeks, binding was mainly associated with connective tissue surrounding primitive nephrons, while at 17 weeks, binding distribution was similar to that in the adult primate kidney, being confined to the glomeruli and smooth muscle of blood vessels, with low binding in the tubules. In fetal monkey adrenal, binding was high in the medulla and connective tissue of the capsule, and low in the zona glomerulosa, while in the adult, binding was high in the zona glomerulosa and medulla. In membrane preparations from fetal monkey skin and skeletal muscle, binding was specific for AII analogs, but in contrast to the adult adrenal, it was not affected by guanyl nucleotides. Scatchard analysis showed a single class of sites with a Kd of 0.6 +/- 0.1 nM and a capacity of 3060 +/- 8.3 fmol/mg, higher than that of the adult adrenal glomerulosa (605 +/- 30 fmol/mg). Specific binding for AII analogs was also present in human fetal skin and skeletal muscle membranes, where Scatchard analysis indicated a Kd of 0.8 nM and a binding capacity of 640 fmol/mg. The transient expression of abundant AII receptors during the phase of rapid growth in the fetus in conjunction with the known effects of AII on cellular growth suggest a role for AII during fetal development in the primate.