Characterization of renal alpha-adrenoceptor subtypes in sheep during development

Abstract

Intrarenal arterial infusion of alpha 1-adrenergic agonists decreases renal blood flow, glomerular filtration rate, and water and sodium excretion to a greater extent in fetus and newborn than in adult sheep. In vitro renal vascular effects of alpha 1- and alpha 2-adrenergic agonists are also greater in fetus than newborn or adult. The present studies were designed to examine the ontogeny of renal alpha-adrenoceptor subtypes in sheep for whom the renal effects of alpha-adrenergic agonists have been described at similar postconceptional ages. With the use of radioligand-binding techniques, specific binding of [3H]prazosin (alpha 1-adrenergic antagonist), [3H]idazoxan, and [3H]rauwolscine (alpha 2-adrenergic antagonists) was studied in fetus, lamb, and adult sheep kidneys. The specific binding of the three radioligands was greatest in fetal and least in adult kidneys. Analysis of Scatchard plots revealed a greater renal alpha 1-adrenoceptor density in fetuses than in lamb or adults. Renal alpha 2-adrenoceptor density was also greater in fetuses than in lambs. These studies suggest that the increased renal alpha 1- and alpha 2-adrenergic effects in fetal sheep are related to increased alpha-adrenoceptor density. Competition experiments and rank adrenergic antagonist potency suggested the presence of only the alpha 1b-adrenoceptor in fetal and adult sheep kidneys. The alpha 2-adrenoceptor that was found only in the fetal sheep had a low affinity to rauwolscine, which is unlike that described in most species for alpha 2-adrenoceptors.