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 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.

Adrenoreactivity of Rat Pial Arteries under Conditions of Stabilized Systemic Blood Pressure

“…Address for correspondence: vshuv@kolt.infran.ru. V. N. ShuvaevaNumerous experiments demonstrated the existence of differentia ted adrenoreactivity in various segments of the same blood vessel or described the development of opposite reactions within the vascular network to norepinephrine [6,[8][9][10]. Our previous detailed analysis of the reaction of consecutive arteries in the precapillary subdivision of the meningeal microcirculatory bed in rats to intravenous norepinephrine also showed that this agent provokes both constrictor and dilator vascular responses [5].…”

“…This determines indirect effects of norepinephrine on blood vessels due to their mechanical distension and activation of the autoregulatory myogenic fl ow-stabilizing mechanisms [3,6]. The use of BP stabilization system [5] decreased the total number and magnitude of the dilator responses, but did not eliminate them completely, which can be explained by the dual action of norepinephrine on α 1 -adrenoceptors evoking constriction and β 2 -adrenoceptors responsible for dilation [6,9,10].The aim of this study was to assess adrenoreactivi ty of pial arteries in various segments (generations) under conditions of systemic BP stabilation against the background of α-and β-adrenoceptor blockade and in the absence of this blockade. …”

“…This determines indirect effects of norepinephrine on blood vessels due to their mechanical distension and activation of the autoregulatory myogenic fl ow-stabilizing mechanisms [3,6]. The use of BP stabilization system [5] decreased the total number and magnitude of the dilator responses, but did not eliminate them completely, which can be explained by the dual action of norepinephrine on α 1 -adrenoceptors evoking constriction and β 2 -adrenoceptors responsible for dilation [6,9,10].…”

Adrenergic reactions in microcirculatory bed of pia mater in rat brain

“…The use of BPSS decreased the total number and amplitude of dilator reactions induced by intravenous NE, although it did not eliminate them entirely, which can be related to NE-induced activation of β 2 -adrenoreceptors responsible for dilation in addition to routine activation of α 1 -adrenoreceptors that trigger vasoconstriction [2,5,6]. Since stabilization of SBP did not suppress the mechanisms of local redistribution of blood supply to the brain, the dilation in one segment of the pial vascular network could be compensatory to constriction of arteries located in other segments of this network.…”

“…For evaluation of the peculiarities of adrenergic regulatory mechanisms, the researchers use sympathomimetic amines such as norepinephrine (NE). However, this agent can induce ambiguous reactions [4][5][6]. The character of the vascular reaction and even its directivity (dilation or constriction) are determined by a number of factors depending on experimental paradigm (species, dosage, the mode of drug administration, specificity in the response of individual segments of vascular bed, etc.)…”