We have shown that maturation increases the magnitude and sensitivity of myogenic reactivity in neonatal cerebral arteries compared to adult mice. Myogenic constriction first appears at 10 mm Hg in cerebral arteries from neonatal mice (5 d) compared to 40 mm Hg in cerebral arteries from adult mice (6-8 wk). Myogenic tone was maintained throughout each step increase in pressure in cerebral arteries from adult mice. In arteries from neonatal nice, myogenic tone was significantly greater at each pressure step compared to response in arteries from adult mice. Wall thickness was similar between groups. In a separate series of experiments, the contractile effect of tetraethylammonium (TEA; a KCa channel blocker) was determined in cerebral arteries from neonatal and adult mice. TEA caused adult and neonatal arteries to constrict; however, constriction in arteries from adult mice was significantly greater compared to arteries from neonatal mice suggesting that KCa channel activity is less in the neonate. Combined, our data suggest that arteries from neonatal mice possess the mechanisms necessary to constrict to increases in pressure. Furthermore, cerebral arteries from neonatal mice develop myogenic tone at lower pressures and to a greater extent compared to arteries from adult mice. Finally, vascular smooth muscle KCa channels modulate myogenic tone in arteries from neonatal mice to a lesser extent compared to arteries from adult mice. These findings have led to the general hypothesis that: maturation decreases the sensitivity and extends the range of pressure-induced myogenic tone of mouse cerebral blood vessels. In order to determine the effects of maturation on myogenic reactivity, pressure, microfluorometry, and electrophysiological experiments will be conducted in arteries taken from newborn (3-5 day) and adult mice (6-8 wk). To determine the relative importance of smooth muscle mechanisms, diameter, intracellular Ca++ and membrane potential experiments will be conducted in endothelium-denuded middle cerebral artery segments. These experiments will enable an unparalleled assessment of the mechanisms whereby maturation affects myogenic reactivity.
