Flow-induced responses in piglet isolated cerebral arteries.

Abstract

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 cerebral artery diameter and pathways by which flow modulates cerebrovascular tone. Arteries from 2-14-d-old piglets were mounted on cannulas and bathed in and perfused with physiologic saline solution. An electronic system controlled pressure and a syringe pump provided constant flow. 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 to 1.60 mL/min (flow/diameter curves). Increasing flow at constant pressure 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 Ca(2+)-free physiologic saline solution; denervated with 6-hydroxydopamine; or treated with indomethacin, N-nitro-L-arginine methyl ester, N omega-nitro-L-arginine (NLA), and L-arginine), ryanodine, or glutaraldehyde. In Na(+)-reduced and in Ca(2+)-free physiologic saline solution, flow constriction was eliminated. Neither indomethacin nor 6-hydroxydopamine affected the biphasic response. N-Nitro-L-arginineL, NLA, and ryanodine blocked dilation, whereas L-arginine restored dilation in NLA-treated arteries. These data suggest that neither prostaglandins nor adrenergic nerve endings participate in flow-induced responses in piglet cerebral arteries. Elimination of flow-constriction by Na+ reduction or Ca2+ removal is consistent with findings in other artery types. The elimination of dilation by N-nitro-L-arginine methyl ester, NLA, and ryanodine suggests that dilation is mediated by nitric oxide and intracellular Ca2+. Whereas the contractile and dilatory responses to agonists remained intact after glutaraldehyde perfusion, both flow-induced constriction and dilation were eliminated, indicating that both types of flow responses result from endothelial cell deformation.