Modulation of Rat Pial Arteriolar Responses to Flow by Glucose

Background: Pial arteriolar responses to flow contribute to regulation of cerebral perfusion and vary according to the transmural pressure to which the vessel is exposed. This study determined the effect of increased glucose concentration on the flow responses of pial arterioles at low and high levels of transmural pressure. Methods: Pial arterioles from Sprague-Dawley rats were mounted in a perfusion myograph. In some arterioles, the endothelium was removed by perfusion with air. Diameters were recorded at transmural pressures of 60 and 120 mmHg during superfusion with physiologic saline containing 5 mM D-glucose, 20 mM D-glucose, or 5 mM D-glucose and 15 mM L-glucose. Diameters during superfusion with saline containing 44 mM D-glucose were measured at an intraluminal pressure of 60 mmHg. Flow-diameter relationships (5-30 μl/min) were recorded during perfusion with the same solutions. Results: Increasing D-glucose concentration caused constriction (P < 0.05) in endothelium-denuded but not in endothelium-intact arterioles. Addition of L-glucose caused constriction in endothelium-intact and -denuded vessels (P < 0.05 for both). At a D-glucose concentration of 5 mM and at low intraluminal pressure, flow elicits endothelium-dependent dilation such that shear stress remains constant. At a D-glucose concentration of 20 or 44 mM, after addition of L-glucose (15 mM), and at high intraluminal pressures, flow elicits constriction and shear stress is unregulated. Conclusions: High glucose concentrations elicit increased basal arteriolar smooth muscle tone that is counteracted by release of endothelium-derived relaxing factors. Endothelium-dependent relaxation to flow (shear stress) is inhibited at high glucose concentrations.