VASCULAR SMOOTH-MUSCLE ACTIN CYTOSKELETON IN CEREBRAL-ARTERY FORCED DILATATION

Background and Purpose-We investigated the role of actin polymerizatio n in regulating arterial diameter in response to increasing pressure a nd modulating forced dilatation of cerebral arteries at pressures abov e the upper limit of autoregulation. Methods-Posterior cerebral arteri es (n=12) were isolated and pressurized in a special arteriograph that allowed control of intravascular pressure and measurement of lumen di ameter. Intact arteries in the absence (control) or presence of 3.0 mu mol/L cytochalasin B (CB), an inhibitor of actin polymerization, were subjected to stepwise increases in pressure from 75 to 200 mm Hg, Lum en diameter was continuously recorded, as was the pressure at which fo rced dilatation (loss of tone) occurred. After a period of time at 200 mm Hg, pressure was returned to 75 mm Hg and the extent of tone recov ery was evaluated. Results-Arteries with and without CB developed a si milar amount of tone during equilibration at 75 mm Hg: percent tone=27 +/-3% for control versus 29+/-4% for CB arteries (P>0.05). However, ar teries in the presence of CB could not withstand pressure as well and underwent FD at significantly lower pressures: 168+/-5 mm Hg for contr ol versus 142+/-5 mm Hg for CB arteries (P<0.01). The amount of tone t hat arteries regained after FD when pressure was returned to 75 mm Hg was also less in CB arteries: percent tone=34+/-3% for control versus 11+/-2% for CB arteries (P<0.01). Conclusions-Cytoskeletal integrity a ppears important for maintaining cerebral arterial diameter during cha nging intravascular pressure. In addition, the process of actin polyme rization may be a significant contributor to development of myogenic t one after forced dilatation.