High flow attenuates relaxation by acetylcholine in isolated perfused canine femoral arteries.

The effect of changes in flow on endothelial-dependent and -independent dilation of isolated perfused arteries was determined. Femoral arteries from ten dogs were excised and mounted in a vessel bath containing a physiological salt solution (PSS) at 37 degrees C, bubbled with 95% O2-5% CO2. The vessel outer diameter was measured using an ultrasonic crystal dimension system. Arteries were perfused with PSS at a steady flow of 1 ml/s at 90 mmHg. Tone was induced in the arteries by the addition of phenylephrine to the vessel bath. Acetylcholine (six dogs) and sodium nitroprusside (four dogs) were added to the perfusate in a cumulative fashion and changes in vessel diameter were recorded until maximum vasodilation was achieved. Dose-response relationships to the agents were determined with each vessel perfused at 1 and 4 ml/s. Sensitivity to each agent was measured as the ED50 value calculated from the respective dose-response relationships. Sensitivity to acetylcholine, but not sodium nitroprusside, was significantly decreased in arteries perfused at 4 ml/s versus 1 ml/s [acetylcholine ED50: 1 ml/s = (0.79 +/- 0.31) x 10(-8) mol/l, 4 ml/s = (1.55 +/- 0.60) x 10(-8) mol/l, P less than 0.05; sodium nitroprusside ED50: 1 ml/s = (2.57 +/- 0.12) x 10(-7) mol/l, 4 ml/s = (2.69 +/- 0.60) x 10(-7) mol/l, not significant]. We conclude that high flow decreases sensitivity to acetylcholine in canine femoral arteries and suggest that vascular reactivity to this agent may be modified by changes in shear on the vascular endothelium.