Pre- and postjunctional 2-adrenergic receptors in fetal and adult ovine cerebral arteries

Bishai, John M., Luit Penninga, Roel Nijland, Rogier Meulenaar, Ciprian P. Gheorghe, Yu Zhao, John N. Buchholz, Lubo Zhang, and Lawrence D. Longo. Preand postjunctional 2-adrenergic receptors in fetal and adult ovine cerebral arteries. Am J Physiol Regulatory Integrative Comp Physiol 282: R1654–R1662, 2002; 10.1152/ajpregu. 00475.2001.—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 2-adrenergic receptor ( 2-AR) density and/or affinity. In fetal ( 140 days) and adult sheep, we measured 2-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 2-AR antagonists yohimbine and idazoxan and contractile responses to the 2-AR agonists clonidine and UK-14304. In fetal and adult cerebral artery homogenates, 2-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 NEinduced 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 2-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, 2-AR appear to be chiefly prejunctional. Nonetheless, the fetal cerebral arteries appear to have a significant component of postjunctional 2-AR.