Impaired Arteriolar Myogenic Reactivity in Early Experimental Diabetes

Hyperperfusion and an increase in capillary pressure has been implicated in the pathogenesis of diabetic microangiopathy. The existence of such alterations suggests that the myogenic response to increased intravascular pressure may be altered in diabetes. To examine this, in vivo studies were performed on the rat cremaster muscle microcirculation of age-matched control and STZ-induced (65 mg/kg) diabetic rats (3–4 wk of diabetes). Anesthetized rats were enclosed in an airtight Plexiglas box with the cremaster muscle exteriorized into an organ bath containing Krebs’ solution. To study myogenic responsiveness, box pressure was increased in steps of 10 mmHg from 0 to 30 mmHg for 2 min. Third-order arterioles of the control animals (lumen diameter 18 ± 2 μm) responded to increased pressure with a rapid onset vasoconstriction. In contrast, the rate of development of the constriction was markedly attenuated in similar vessels (15 ± 1 μm) of the diabetic animals, despite their ability to exhibit a similar maximal arteriolar constriction to that of the control animals. When 20 mmHg pressure steps were applied for only 10 s, arterioles of the diabetic animals constricted minimally, whereas those of the control animals constricted to 75% of the maximal response expected for that pressure increase (P < 0.01). Second-order arterioles of both groups of animals responded with a primarily passive distension to increased intravascular pressure suggesting that the impaired responsiveness of the third-order arterioles is not compensated for by an increase in the myogenic responsiveness of upstream vessels. Basal intravascular pressures, measured in first-, second-, and third-order arterioles, were similar in control and diabetic animals. These data suggest that experimental diabetes is associated with an impairment in the rate of development of myogenic vasoconstriction in precapillary arterioles that may predispose the capillary bed to transient episodes of elevated pressure.