The blood vessel, linchpin of diabetic lesions

The morbidity and mortality associated with diabetes mellitus are essential ly related to the vascular lesions that develop over time in this condition . Both the macrocirculation and microcirculation are involved, and as a con sequence, vital organs such as the brain, retina, heart, and kidney and the limbs become damaged, Because microalbuminuria represents the earliest and probably most sensitive indication of endothelial dysfunction in diabetes mellitus, the results of pharmacologic intervention with angiotensin-conver ting enzyme inhibitors, which treat glomerular hypertension were the first indication of potential beneficial effects in reducing diabetic nephroplast y. The nature of endothelial dysfunction related to diabetes is probably no t homogeneous, since microcirculation networks are affected at different pe riods and with variable intensity. This appears to be the case for the aort a, the heart, segments of the digestive tract; the skin, and the skeletal m uscle, the largest consumer of insulin. Although the aorta and large arteri es contain a small portion of the total blood volume, their distribution of blood flow (pulse pressure) to peripheral organs may affect endothelial fu nction in the microcirculation. Changes in the structure of conduit arterie s, partly responsible for the alteration in compliance characteristics, cou ld well be related to the way these arteries are fed by the vasa vasorum sy stem. This report describes a new in vitro approach to examine capillary pe rmeability in normal and alloxan-induced diabetic rabbits. Preliminary resu lts indicate that the size of terminal arterioles of the vasa vasorum (incr eased diameter) and the capillary permeability to albumin (markedly enhance d) in this specialized network are profoundly affected in the thoracic aort a obtained from diabetic animals, Albumin extravasation into the interstiti al fluid compartment of the aorta is likely to lead to structural and physi cochemical changes: in fact, removal of interstitial macromolecules via lym phatic drainage is poor in the blood: Vessel wall of large arteries. This e xperimental approach is likely to be useful in the exploration of medicatio ns affecting the structure and function of conduit vessels. Copyright (C) 1 999 by W.B. Saunders Company.