Microvascular Reactivity to Norepinephrine at Different Arteriolar Levels and Durations of Streptozocin-Induced Diabetes

Microvascular disease is a hallmark of diabetes. Although the etiology of diabetic microangiopathy remains to be elucidated, numerous studies in experimental animals and human diabetic patients have suggested that a change in vascular reactivity to vasoactive agents is a component of the pathophysiology. Most previous studies have utilized indirect methods to study the microcirculation or have conducted studies of responses in large vessels. This study was designed to directly study in an intact microvascular preparation the effects of streptozocin-induced diabetes (STZ-D) on microvascular reactivity. The responses of arterioles in the cremaster muscle of pentobarbital sodium-anesthetized rats to topically applied norepinephrine were measured in STZ-D rats of 2, 4, 8, 16, and 32 wk duration and in age-matched nondiabetic rats. Resting arteriolar diameters and mean arterial pressure were not affected by diabetes. In the STZ-D rats, larger (1A) arterioles were normally responsive after 2, 4, 8, and 16 wk of diabetes compared with nondiabetic rats. In contrast, the smaller 2A and 3A arterioles exhibited hypersensitivity to norepinephrine initially, but responses returned to normal sensitivity as the duration of diabetes progressed to the chronic stage. These results suggest that there are important functional changes in the responses of the microcirculation to norepinephrine that are associated with the development of diabetes and that these changes are anatomically specific and temporally dependent.