Ontogeny of Angiotensin II Type 1 Receptor mRNAs in Fetal and Neonatal Rat Brain: Implications for Systemic Cardiovascular Control

Abstract 333 Poster Session I, Saturday, 5/1 (poster 160)

Angiotensin II (AngII) type 1 receptor (AT₁) plays a critical role in central cardiovascular and fluid regulation and exerts a predominant function in fetal and neonatal cardiovascular homeostasis. AngII also modulates arterial baroreflex during neonatal but not fetal life. Ontogenic changes in AT₁ transcripts during early brain development are currently unknown. Using radiolabeled cRNA probes for in situ hybridization histochemistry, we determined the ontogeny of the two AT₁ subtypes (AT_1a and AT_1b) expression in fetal and neonatal rat brain, from 11 days of gestation (E11) to 28 days postnatal (P28). Brain AT_1a mRNA is first detected at E19. The age of appearance of AT_1a mRNA varies among different brain areas and overall expression predominates in areas involved in fluid homeostasis and cardiovascular regulation where it persists until P28. Among these areas, AT_1a mRNA is present starting at E19 in the median preoptic nucleus, the vascular organ of the lamina terminalis, the paraventricular nucleus, and very weakly in the nucleus of the solitary tract. At E21 AT_1a mRNA expression appears in the subfornical organ, which is key relay structure in fluid and salt homeostasis. Fetal expression of AT_1a mRNA was also noted in other brain areas starting at E19 in the periaqueductal gray matter, the nucleus raphe pallidus and the motor facial nucleus and at E21 in the anterior olfactory nucleus and the piriform cortex. Expression of AT_1a mRNA appears only after birth in many regions involved in cardiovascular central modulation such as the lateral hypothalamic areas, the area postrema and medullary reticular nuclei. Other brain areas expressing AT_1a mRNA only after birth include telencephalic olfactory structures, the substantia nigra, many preoptic areas, the ventral tegmental area, the pedunculopontine nucleus, and the nucleus of the lateral lemniscus. Certain structures express transiently AT_1a mRNA during development like the red nucleus, the substantia nigra and the nucleus of the lateral lemniscus. No detectable amount of AT_1b mRNA was present in the fetal and neonatal rat brain. Our results generally correlate with autoradiographic AT₁ binding site studies performed during the perinatal period. In conclusion, expression of AT_1a mRNA during brain development appears in late gestation at E19, predominates in forebrain areas involved in fluid homeostasis and cardiovascular regulation. In contrast, expression remains very weak to absent until after birth in many medullary nuclei known to play an important role in cardiovascular modulation. Our results support a role of AT_1a during perinatal life in fluid and perhaps cardiovascular homeostasis and suggest that the medullary cardiovascular modulation by AngII would mature later during postnatal life.