Neural regulation of submandibular gland blood flow in the streptozotocin-diabetic rat: evidence for impaired endothelium-dependent vasodilatation

Functional changes in vascular tone and reactivity arise early in diabetes, and endothelial dysfunction plays a central role in the development of these microvascular abnormalities. Blood flow in the rat submandibular gland is mainly under neural regulation, which is mediated in part via endothelium-dependent mechanisms. Given the role of the endothelium in regulating blood flow and the deleterious effects of diabetes on endothelial cell function, we hypothesised that diabetes would significantly impair neural regulation of submandibular gland vascular perfusion. Three weeks after the induction of streptozotocin diabetes continuous 2 Hz sympathetic stimulation resulted in a similar degree of vasoconstriction (as measured by a decrease in perfusion) in both diabetic (−31±17%) and control rats (−22±7%). However, the magnitude and the duration of the after-dilatation were significantly less in diabetic animals. The same number of impulses delivered at 20 Hz in bursts (1 s in every 10 s) also resulted in vasoconstriction with each burst, but unlike the effects of burst stimulation in control rats the initial vasoconstriction was not converted to a net vasodilatation between bursts. Parasympathetic stimulation (2, 5 and 10 Hz) caused a marked vasodilatation in both control and diabetic rats, but the initial responses were delayed in diabetic animals, the maintained phases were smaller in magnitude (P<0.02) and it took longer to return to resting levels. In conclusion, submandibular gland vascular responses are altered in streptozotocin-induced diabetic rats. Vasoconstrictor responses evoked by sympathetic impulses were unaffected, but vasodilatory responses, particularly those associated with endothelium-dependent mechanisms, were significantly reduced.