EFFECTS OF MATURATION ON ALPHA-ADRENERGIC RECEPTOR AFFINITY AND OCCUPANCY IN SMALL CEREBRAL-ARTERIES

The present experiments examine the hypothesis that changes in recepto r affinity and occupation mediate maturational changes in norepinephri ne sensitivity in small cerebral arteries. In second-order (2B) and fo urth-order (4B) branch middle cerebral artery segments from newborn an d adult sheep, we first found that a stretch ratio based on artery dia meter better estimated optimal prestretch than did passive tension. Ne xt, we determined norepinephrine dose-response relations before and af ter pratosin, yohimbine, and benextramine. Prazosin competitively bloc ked contractions to norepinephrine, but yohimbine had no effect, indic ating that alpha(1)-adrenoceptors mediated contraction. Norepinephrine sensitivity [determined from the -log of the half-maximal effective d ose (pD(2))], maximal response, and binding affinity all decreased wit h age in 4B but not 2B segments. Receptor occupancy at the pD(2) incre ased with age only in 2B segments. In conclusion, maturation of ovine middle cerebral arteries involves branch-specific changes in affinity and receptor occupation of the alpha(1)-adrenoceptors that mediate con tractile responses to norepinephrine. Age-related changes in receptor density and/or intrinsic efficacy probably are involved also.