Developmental Regulation of the α1B-Adrenoceptor in the Sheep Kidney

Abstract

ABSTRACT. The expression of renal ale-adrenoceptor (alB-AR) mRNA was studied and contrasted with the expression of renal renin mRNA in fetal and newborn sheep. Fetal sheep between 90 and 91, 116 and 118, and 139 and 141 d gestation (term is 145 d gestation) as well as newborn lambs between 1 and 2 d old and 8 and 10 d old were studied (n = 3 for each age range). The role of the renal nerves in regulating changes in ale-AR gene expression was also investigated by measuring renal cortical ale-AR mRNA levels and receptor kd and maximum number of binding sites in 24-h-old lambs that were either denervated (n = 6) or sham-operated (n = 5) 3 d before birth. During development, renal aIB-AR mRNA levels show a marked increase in term fetuses; this increase persists into the first 2 d of life and is distinct from the developmental pattern seen for renal renin mRNA levels. Denervation of term fetuses does not alter the expression of renal a,B-AR mRNA in newborn lambs when compared with sham-operated controls but decreases significantly the expression of the renin gene (p < 0.05). These results suggest that the ale-AR gene is developmentally regulated in the kidney in a pattern distinct from that seen for renin. Furthermore, the renal nerves, which play an important role in the regulation of renin gene expression at the time of birth, do not appear to be an important factor in the regulation of the als-AR during the maturation from fetal to newborn life. (Pediatr Res 34: 124-1 28, 1993) Abbreviations UIB-AR, UIB-adrenoceptor GAPD, glyceraldehyde-3-phosphate dehydrogenase B, ., maximum number of binding sites Previous studies ( I ) have suggested that stimulation of aadrenoceptors modulates renal hemodynamics and fluid and electrolyte homeostasis during development. For example, the renal and vasoconstrictor response to intrarenal infusion of phenylephrine (2), an al-adrenoceptor agonist, or to low-frequency renal nerve stimulation (3, 4) is greater in the near-term sheep fetus than in the newborn lamb. Similarly, fetal and newborn sheep show a greater antinatriuretic response to renal al-adrenergic stimulation than do older animals (5). It has also been shown that renal nerves modulate the natriuretic response to volume expansion in fetal and newborn animals (6) and that renal denervation before birth increases renal sodium excretion in the immediate postnatal period (7). Furthermore, studies in sheep (8) have demonstrated that renal nl-adrenoceptor density (B,,,) and affinity (kd) are greater in near-term sheep fetuses than in I-wk-old lambs and older sheep, suggesting that the changing responses to renal nerve stimulation and cul-adrenoceptor stimulation observed during renal maturation may be due to changes in al-adrenoceptors.In an effort to elucidate further the mechanisms regulating the developmental changes in renal nl-adrenoceptors. the present study was designed to determine the ontogenic changes in R I B -AR mRNA expression in the sheep, because the ale-AR is the predominant nl-adrenoceptor in the sheep renal ...