The Effect of Insulin Treatment on Changes in Vascular Reactivity in Chronic, Experimental Diabetes

The influence of insulin treatment on the reactivity of aortae and mesenteric arteries from rats with chronic streptozocin (STZ)-induced diabetes was examined. Ninety days after the onset of diabetes, the responsiveness (developed tension [g]/cross-sectional area of tissue [mm2] ) but not the sensitivity (pD2 value) of both aortae and mesenteric arteries from untreated rats to norepinephrine (NE) was significantly increased compared with age-matched, nondiabetic controls. However, responses of K+-depolarized preparations from untreated diabetic rats to increasing extracellular Ca2+ were unchanged. Treatment of diabetic animals with daily injections of insulin for 90 days, starting 3 days after STZ treatment, normalized blood glucose levels and body weights and completely prevented the increases in responsiveness of aortae and mesenteric arteries to NE. No significant differences in systolic blood pressures, measured at weekly intervals, could be detected between nondiabetic, untreated diabetic, and insulin-treated diabetic rats. Insulin treatment of diabetic animals for 30 days, begun 90 days after the onset of diabetes, also normalized blood glucose levels and completely reversed the increases in the responsiveness of aortae and mesenteric arteries to NE. These results indicate that selective increases in the reactivity of aortae and mesenteric arteries to NE occur in diabetic rats before the development of hypertension. The ability of chronic insulin treatment to restore vascular responsiveness to NE to control levels suggests that the increased reactivity is a consequence of the diabetic state, and may predispose animals to the subsequent development of hypertension.