Alteration of microvascular responses to serotonin in the diabetic rat

This study examined the microvascular response to serotonin (5-hydroxytryptamine; 5-HT) in short-term streptozotocin-induced diabetic rats. 5-HT was applied topically to the neurovascularly intact and environmentally controlled cremaster muscle of the two-week diabetic rat. Intravital microscopy was used to measure the diameters of large arterioles (First-order; A1) and small arterioles (Third-order; A3), and the FITC-albumin leakage in small venules (Third-order; V3). The diabetic animals were divided into two groups based on the dilator capacity of the A3 arterioles: the Diabetic-Tone group had a dilator capacity of 98 +/- 14.5% compared to 11 +/- 4.1% for the Diabetic No-Tone animals. 5-HT caused significantly greater constriction of A1 arterioles in Diabetic-Tone animals (-40 +/- 6%) than in either the Control (-19 +/- 6%) or Diabetic No-Tone (-18 +/- 5%) animals. 5-HT dilated the A3 arterioles to a similar degree in both the Diabetic-Tone and Control groups, but the Diabetic No-Tone group did not dilate to 5-HT because the A3 arterioles in these animals possessed no basal tone. Control animals showed a large 5-HT concentration-dependent increase in leakage of albumin in V3 venules, but this response was inhibited in the Diabetic-Tone animals. The 5-HT-induced leakiness in the Diabetic No-Tone group was intermediate between the other two groups. These results show that large arteriole constriction and small venule permeability responses to 5-HT are altered early in the development of diabetes, and are different in those animals with and without basal arteriolar tone. These data suggest that streptozotocin-induced diabetes alters microvascular function in striated muscle by at least two different cellular mechanisms.