Albumin escape from microvessels in kidney, heart and skeletal muscle in experimental diabetes mellitus in the anaesthetized rat.

Diabetes was induced with streptozotocin in rats weighing about 160 g. These were maintained with age-matched controls for up to 14 months, blood glucose being periodically monitored. Half the diabetic and control rats received the aldose reductase inhibitor, Ponalrestat, in their diet. Distribution of volumes of 131I-albumin (5 min) and 125I-albumin (100 min) were estimated in various tissues at 3 weeks, 6-7 months and 13-14 months of diabetes. The former space was assumed to represent the intravascular plasma space, while the latter was taken to include both the extravascular and intravascular albumin volumes in the kidney. In heart and skeletal muscle, equilibration between the specific activities of extravascular albumin and of plasma albumin was not assumed to be complete at 100 min. In the cortex and medulla of kidney, the extravascular albumin pool increased significantly at 13-14 months of diabetes (for both, P less than 0.01). Significantly increased entry of albumin into the interstitium occurred at 6 months (P less than 0.05) and at 13-14 months (P less than 0.01) in skeletal muscle, and at 13-14 months (P less than 0.05) in heart. The intravascular plasma volumes were not influenced by diabetes and the aldose reductase inhibitor had no effect at any time in either diabetic or control rats. These findings indicate increased movement of plasma albumin into the interstitium in the late phase of diabetes in the heart, skeletal muscle and in the kidney. Enlargement of the interstitial albumin pool is likely to affect the fluid balance between capillary and interstitium and may contribute to the effect of diabetes on the function of these organs.