Increased capillary permeability to albumin in diabetic rat myocardium.
To clarify the mechanism for the well-known increase in microvascular permeability that occurs with diabetes mellitus, we investigated capillary permeability to albumin in diabetic rat myocardium by electron microscopy using albumin-gold (Alb-Au) complexes as a tracer. Diabetes was induced by an intravenous injection of streptozotocin. After 24-32 weeks, hearts from diabetic rats and age-matched control rats were perfused with Krebs-Henseleit bicarbonate buffer containing Alb-Au for 5 or 20 minutes and then fixed and processed for electron microscopy. The binding and transport of Alb-Au by capillary endothelium was quantitatively evaluated. In control rats, Alb-Au particles were found preferentially bound to the luminal plasmalemmal vesicles. In diabetic rats, the labeling of luminal vesicles was more extensive and more pronounced after 5 minutes of perfusion when compared with control vesicles. The plasma membrane proper was also heavily labeled in diabetic rats. After 20 minutes, Alb-Au particles were transported across the capillary endothelium via plasmalemmal vesicles, but they did not penetrate the intercellular junctions in either control or diabetic rats. The vesicular transport of Alb-Au across the capillary endothelium was significantly increased in the diabetic myocardium when compared with control myocardium (percentage of abluminal labeled vesicles, 25.9 +/- 5.5% versus 1.3 +/- 0.5%; p < 0.01). The study on food-restricted rats with body weights close to those of diabetic rats suggested that caloric deficiency alone did not have much effect on capillary permeability. The data indicate that capillary permeability to albumin is markedly increased in diabetic myocardium because of enhanced vesicular transport. This may play an important role in the pathogenesis of diabetic cardiomyopathy.
Yamaji
T
T
First Department of Internal Medicine, Shiga University of Medical Science, Japan.
Fukuhara
T
T
Kinoshita
M
M
D000818:Animals; D001808:Blood Vessels / Q000648:ultrastructure; D002199:Capillary Permeability; D002908:Chronic Disease; D003326:Coronary Circulation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D002149:Energy Intake; D006046:Gold; D008297:Male; D008854:Microscopy, Electron; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism*
D012709:Serum Albumin; D006046:Gold