IMPAIRED ARTERIOLAR MYOGENIC REACTIVITY IN EARLY EXPERIMENTAL DIABETES

Hyperperfusion and an increase in capillary pressure has been implicat ed in the pathogenesis of diabetic microangiopathy. The existence of s uch alterations suggests that the myogenic response to increased intra vascular pressure may be altered in diabetes. To examine this, in vivo studies were performed on the rat cremaster muscle microcirculation o f age-matched control and STZ-induced (65 mg/kg) diabetic rats (3-4 wk of diabetes). Anesthetized rats were enclosed in an airtight Plexigla s box with the cremaster muscle exteriorized into an organ bath contai ning Krebs' solution. To study myogenic responsiveness, box pressure w as increased in steps of 10 mmHg from 0 to 30 mmHg for 2 min. Third-or der arterioles of the control animals (lumen diameter 18 +/- 2 mum) re sponded to increased pressure with a rapid onset vasoconstriction. in contrast, the rate of development of the constriction was markedly att enuated in similar vessels (15 +/- 1 mum) of the diabetic animals, des pite their ability to exhibit a similar maximal arteriolar constrictio n to that of the control animals. When 20 mmHg pressure steps were app lied for only 10 s, arterioles of the diabetic animals constricted min imally, whereas those of the control animals constricted to 75% of the maximal response expected for that pressure increase (P < 0.01). Seco nd-order arterioles of both groups of animals responded with a primari ly passive distension to increased intravascular pressure suggesting t hat the impaired responsiveness of the third-order arterioles is not c ompensated for by an increase in the myogenic responsiveness of upstre am vessels. Basal intravascular pressures, measured in first-, second- , and third-order arterioles, were similar in control and diabetic ani mals. 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 t ransient episodes of elevated pressure.