Responses to pulsatile flow in piglet isolated cerebral arteries.

Because cerebrovascular hemorrhage in newborns is often associated with fluctuations in cerebral blood flow, this study was designed to investigate the effects of pulsatile flow in isolated cerebral arteries from neonatal piglets. Arteries mounted on cannulas were bathed in and perfused with a physiologic saline solution. An electronic system produced pulsations, the amplitude and frequency of which were independently controlled. At constant mean transmural pressure (20 mm Hg), increasing flow in steps from 0 to 1.6 mL/min under steady flow conditions caused a biphasic response, constriction at low flow, and dilation at high flow. Under pulsatile flow conditions (pulse amplitude 16-24 mm Hg; 2 Hz), the arteries dilated upon flow initiation and continued to dilate as mean flow increased. Dilation to pulsatile flow did not depend on the level of mean flow because switching from steady to pulsatile flow at each flow step also caused dilation. Arteries dilated further upon increasing either pulse amplitude (12-28 mm Hg; 2 Hz) or frequency (16-24 mm Hg; 4 Hz). Inhibiting nitric oxide synthesis with Nomega-nitro-L-arginine or perfusing with glutaraldehyde to decrease endothelial cell deformability significantly reduced dilations to pulsatile flow and to increased amplitude and frequency. These data suggest that the arterial response to flow is highly dependent on the mode of flow. Dilation induced by initiating pulsatile flow or increasing either pulse amplitude or frequency appears to be mediated by augmented nitric oxide release as result of shear stress-induced deformation of the endothelial cells.

Flow-induced responses in cat isolated pulmonary arteries.

Isolated, cannulated, endothelium-intact cat pulmonary arteries, averaging 692 +/- 104 microns in diameter, were set at a transmural pressure of 10 mmHg and monitored with a video system. Intraluminal flow was increased in steps from 0 to 1.6 ml/min by using a syringe pump. An electronic system held pressure constant by changing outflow resistance. Flow-diameter curves were generated in physiological saline solution. At constant transmural pressure, the arteries constricted in response to increased intraluminal flow. Constriction was not affected by removing extracellular Ca2+ but was abolished after treatment with ryanodine to deplete intracellular Ca2+ stores, with the endothelin-1 synthesis inhibitor phosphoramidon, with the endothelin A-receptor antagonist BQ-123, with the protein kinase C inhibitor staurosporine, or with glutaraldehyde to reduce endothelial cell deformability. The results indicate that isolated pulmonary arteries can constrict in response to intraluminal flow and suggest that constriction is mediated by endothelin-1 and depends on intracellular Ca2+ release and protein kinase C activation.

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 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.

Effects of indomethacin on myogenic contractile activation and responses to changes in O2 and CO2 in isolated feline cerebral arteries.

We used an isolated, pressurized, and perfused feline middle cerebral artery preparation to measure how changes in intraluminal pressure and alterations in O2 and CO2 affect vessel diameter and myogenic contractile activation before and after treatment with indomethacin (IND). Vessel diameters were measured over the pressure range 60-140 mm Hg. The arteries were then exposed to low O2 (50 torr) and/or high CO2 (65 torr) and diameters remeasured over the same range. Under control conditions, the arteries exhibited myogenic contractile activation. Exposure to low O2, high CO2, or a mixture of low O2/high CO2, increased vessel diameter but did not change the vessels' myogenic contractile responsiveness to changes in pressure. Arteries exposed to IND decreased in diameter but retained myogenic contractile activity. In the presence of IND, vessels dilated to both low O2 and a mixture of low O2/high CO2, but did not dilate to high CO2 alone. Under all conditions, vessels retained myogenic contractile activity. Results obtained under control conditions and low O2 confirm those of others using similar systems. Myogenic contractile activity in the presence of high CO2 or a mixture of low O2/high CO2 has not been previously reported. The dilation to low O2 but not to high CO2 in the presence of IND suggests that this drug's effects in cerebral arteries are not limited solely to inhibition of prostaglandin synthesis.