Does the endothelium play a role in flow-dependent constriction? A study in the isolated rabbit femoral artery

We studied the role of the endothelium in diameter changes as a function of flow of the isolated femoral artery of the rabbit (n = 15) perfused and superfused with a physiological salt solution (37 degrees C). In 10 vessels, diameters were studied before and after exposure to gossypol, an agent that impairs the endothelial function pharmacologically. In 5 of these 10 vessels we added albumin (1.5%) to the perfusion solution. The mean external diameter (+/- SEM) after equilibration for 60 min at a transmural pressure of 50 cm H2O (n = 10) was: 1,426 +/- 34 microns. Vessels were then constricted with norepinephrine (1.0-1.5 microM in the superfusion solution) to 70% of the resting diameter, acetylcholine was used to check endothelial function. All vessels constricted as flow was increased (p less than 0.001), irrespective of the impairment of the endothelial function by gossypol or the presence of albumin. It is therefore unlikely that the flow-induced constriction results from a 'wash away' effect of endothelium-derived relaxing factor (EDRF). To test whether EDRF could still play a role after gossypol, we used hemoglobin (n = 5) to bind EDRF. Flow-dependent constriction was still observed, although the mean diameter was decreased. We conclude that flow-dependent constriction is either mediated via the endothelial cells, but not via EDRF, or that the endothelial cells are not involved.