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

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2002-06, Vol.282 (6), p.R1654
• Main Authors: Bishai, John M, Penninga, Luit, Nijland, Roel, Meulenaar, Rogier, Gheorghe, Ciprian P, Zhao, Yu, Buchholz, John N, Zhang, Lubo, Longo, Lawrence D
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Age Factors; Animals; Binding, Competitive - drug effects; Brimonidine Tartrate; Cerebral Arteries - chemistry; Cerebral Arteries - drug effects; Cerebral Arteries - embryology; Cerebral Arteries - metabolism; Clonidine - pharmacology; Dose-Response Relationship, Drug; Female; Fetus; Idazoxan - pharmacology; Middle Cerebral Artery - drug effects; Middle Cerebral Artery - embryology; Middle Cerebral Artery - metabolism; Norepinephrine - pharmacology; Phenylephrine - pharmacology; Pregnancy; Quinoxalines - pharmacology; Receptors, Adrenergic, alpha-2 - metabolism; Sheep; Tetrodotoxin - pharmacology; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vasoconstrictor Agents - pharmacology; Yohimbine - pharmacology
• ISSN: 0363-6119
• DOI: 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 alpha(2)-adrenergic receptor (alpha(2)-AR) density and/or affinity. In fetal (approximately 140 days) and adult sheep, we measured alpha(2)-AR density and affinity with the antagonist [(3)H]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 alpha(2)-AR antagonists yohimbine and idazoxan and contractile responses to the alpha(2)-AR agonists clonidine and UK-14304. In fetal and adult cerebral artery homogenates, alpha(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 pD(2) for NE-induced tension in the presence of 3 x 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 pD(2) 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 alpha(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, alpha(2)-AR appear to be chiefly prejunctional. Nonetheless, the fetal cerebral arteries appear to have a significant component of postjunctional alpha(2)-AR.