Vessel-Specific Regulation of Angiotensin II Receptor Subtypes During Ovine Development

Abstract

Umbilical and systemic responses to angiotensin II differ in term fetal sheep, and peripheral vascular responses are attenuated or absent before and after birth. These observations may reflect developmental differences in angiotensin II receptor (AT) subtypes in vascular smooth muscle (VSM). Studies of AT subtype ontogeny and regulation are generally limited to the aorta, which may not be extrapolated to other arteries, and neither is completely described during ovine development. We therefore characterized VSM AT subtype expression and regulation throughout an extended period of development in umbilical and carotid artery and aorta from fetal (85-146 d gestation), postnatal (5-23 d), and adult sheep, measuring AT(1) and AT(2) mRNA and protein and performing immunohistochemistry. Parallel increases in umbilical AT(1) mRNA and protein began early in gestation and continued to term, and although AT(2) mRNA was unchanged, protein levels decreased >90% at term. Fetal carotid AT(1) mRNA was <40% of adult values and unchanged before birth; however, AT(1) protein rose >2-fold at term. After birth, AT(1) mRNA increased to 85% of adult values and was associated with another 2-fold rise in protein. In contrast, carotid AT(2) mRNA and protein fell in parallel throughout development and were barely detectable in the newborn and the adult. Immunostaining was consistent with observations in both arteries. A third pattern occurred in aortic VSM. The ontogeny of AT subtype expression and regulation is vessel specific, with changes in umbilical VSM beginning very early in development. Although the mechanisms that regulate mRNA and protein expression are unclear, these changes parallel differences in VSM maturation and function and local blood flow.