The Effect of Alloxan-Induced Diabetes on Tissue Plasminogen Activator Activity of the Rat

Subcutaneous injection of alloxan (10mg/100g)induced severe diabetes in Sprague-Dawley rats (hyperglycemia, glucosuria, weight loss, polydypsia, polyphagia and polyuria). The effect on tissue plasminogen activator activity (PAA) was studied histocheraically in key organs (heart, kidney, lung, aorta, and caudal vena cava) 4 days, 2, 3, 4, 6, and 8 weeks after induction of diabetes. After an initially increased vascular PAA (release reaction) seen in lung, kidney, aorta, and myocardium, but not in caudal vena cava, a decreased PAA was found in arteries of the renal medulla and particularly of the renal cortex and in arteries of the myocardium two bo eight weeks after the induction of diabetes. Compared to the normal PAA level, the intima of the aorta showed after the initial rise, a fall in two to three weeks, a second rise by four to six weeks, followed by a fall to the normal value at the eighth week. In the lung the initially increased PAA continued to be slightly elevated until the sixth week; by the eighth week it was normal. In the caudal vena cava no changes in the PAA were seen. Of interest are the observed differences in PAA patterns; (1) between arteries and veins, (2) large and small arteries, and (3) arteries in different tissues up to at least eight weeks post induction of diabetes.Supp-. by the Austrian Acad, of Sciences, Arteriosclerosis research group.