Effects of maturation on adrenergic neurotransmission in ovine cerebral arteries

The present studies examine the hypothesis that multiple adrenergic neuroef fector mechanisms are not fully developed in fetal, compared with adult, ov ine middle cerebral arteries. In arteries denuded of endothelium and pretre ated with 1 mu M atropine to block involvement of muscarinic receptors, 10 mu M capsaicin to deplete sensory peptidergic neurons, and 10 mu M nitro-L- arginine methyl ester (L-NAME) to block. possible influences from nitric ox idergic innervation, transmural stimulation at 16 Hz increased contractile tensions to 9.5 +/- 3.7% (n = 6) of the potassium maximum in adult arteries . Corresponding values in fetal arteries, however, were significantly less and averaged only 1.1 +/- 0.6% (n = 10). However, postsynaptic sensitivity to norepinephrine (NE) was similar in the two age groups; NE pot values (-l og EC50) averaged 6.11 +/- 0.12 (n = 6) and 6.33 +/- 0.09 M (n = 9) in feta l and adult arteries, respectively. Similarly, NE content measured via HPLC was also similar in the two age groups and averaged 32.4 +/- 5.0 (n = 17) and 32.5 +/- 3.9 ng/ng wet wt (n = 13) in fetal and adult middle cerebral a rteries, respectively. In contrast, stimulation-induced NE release was grea ter in fetal than in adult arteries, whether calculated as total mass relea sed [883 +/- 184 (n = 17) vs. 416 +/- 106 pg NE/mg wet wt (n = 13)] or as f ractional release [51.1 +/- 5.3 (n = 17) vs. 22.8 +/- 3.8 pg/pg NE content per pulse x 10(-6)]. Measured as an index of synaptic density, neuronal coc aine-sensitive NE uptake was similar in fetal and adult arteries [1.55 +/- 0.40 (n = 10) and 1.84 +/- 0.51 pmol/mg wet wt (n = 7), respectively]. Over all, age-related differences in postsynaptic sensitivity to NE, NE release, and NE uptake capacity cannot explain the corresponding age-related differ ences in response to stimulation. The data thus suggest that total synaptic volume and cleft width, in particular, are probably greater and/or that ad renergic corelease of vasoactive substances other than NE is altered in fet al compared with adult middle cerebral arteries.