FLOW-INDUCED RESPONSES IN PIGLET ISOLATED CEREBRAL-ARTERIES

Although cerebral hemorrhage is a widely occurring neurologic disorder thought to be caused by fluctuating blood flow, the response to flow in the neonatal cerebrovasculature has not been characterized. In the present study, we examined the effect of changing flow on middle cereb ral artery diameter and pathways by which flow modulates cerebrovascul ar tone. Arteries from 2-14-d-old piglets were mounted on cannulas and bathed in and perfused with physiologic saline solution. An electroni c system controlled pressure and a syringe pump provided constant how. The transmural pressure was held constant at 20 mm Hg, and changes in vessel diameter were measured as flow was increased in steps from 0 t o 1.60 mL/min (flow/diameter curves). Increasing flow at constant pres sure resulted in constriction at flows from 0.077 to 0.152 mL/min and dilation at flows from 0.212 to 1.60 mL/min. The flow/diameter curves were repeated in arteries bathed in Na+-reduced or Ca2+-free physiolog ic saline solution; denervated with 6-hydroxydopamine; or treated with indomethacin, N-nitro-L-arginine methyl ester, N-omega-nitro-L-argini ne (NLA), and L-arginine), ryanodine, or glutaraldehyde. In Na+-reduce d and in Ca2+-free physiologic saline solution, flow constriction was eliminated. Neither indomethacin nor S-hydroxydopamine affected the bi phasic response. N-Nitro-L-arginineL, NLA, and ryanodine blocked dilat ion, whereas L-arginine restored dilation in NLA-treated arteries. The se data suggest that neither prostaglandins nor adrenergic nerve endin gs participate in flow-induced responses in piglet cerebral arteries. Elimination of flow-constriction by Na+ reduction or Ca2+ removal is c onsistent with findings in other artery types, The elimination of dila tion by N-nitro-L-arginine methyl ester, NLA, and ryanodine suggests t hat dilation is mediated by nitric oxide and intracellular Ca2+ Wherea s the contractile and dilatory responses to agonists remained intact a fter glutaraldehyde perfusion, both flow-induced constriction and dila tion were eliminated, indicating that both types of how responses resu lt from endothelial cell deformation.