Pre- and postjunctional α2-adrenergic receptors in fetal and adult ovine cerebral arteries

Abstract

In ovine cerebral arteries, adrenergic-mediated vasoconstrictor responses differ significantly with developmental age. We tested the hypothesis that, in part, these differences are a consequence of altered α2-adrenergic receptor (α2-AR) density and/or affinity. In fetal (∼140 days) and adult sheep, we measured α2-AR density and affinity with the antagonist [3H]idazoxan in main branch cerebral arteries and other vessels. We also quantified contractile responses in middle cerebral artery (MCA) to norepinephrine (NE) or phenylephrine in the presence of the α2-AR antagonists yohimbine and idazoxan and contractile responses to the α2-AR agonists clonidine and UK-14304. In fetal and adult cerebral artery homogenates, α2-AR density was 201 ± 18 and 52 ± 6 fmol/mg protein, respectively (P < 0.01); however, antagonist affinity values did not differ. In fetal, but not adult, MCA, 10-7 M yohimbine significantly decreased the pD2 for NE induced tension in the presence of 3 × 10-5 M cocaine, 10-5 M deoxycorticosterone, and 10-6 M tetrodotoxin. In fetal, but not adult, MCA, UK-14304 induced a significant decrease in pD2 for the phenylephrine dose-response relation. In addition, stimulation-evoked fractional NE release was significantly greater in fetal than in adult cerebral arteries. In the presence of 10-6 M idazoxan to block α2-AR-mediated inhibition of prejunctional NE release, the fractional NE release was significantly increased in both age groups. We conclude that in fetal and adult ovine cerebral arteries, α2-AR appear to be chiefly prejunctional. Nonetheless, the fetal cerebral arteries appear to have a significant component of postjunctional α2-AR.