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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1361-1368.)
© 1997 American Heart Association, Inc.

Articles

Changes With Age in the Influence of Endogenous Nitric Oxide on Transport Properties of the Rabbit Aortic Wall Near Branches

Beverley A. Forster; ; Peter D. Weinberg

From the School of Animal and Microbial Sciences, University of Reading, Reading, United Kingdom.

Correspondence to Dr P.D. Weinberg, School of Animal and Microbial Sciences, University of Reading, Whiteknights PO Box 228, Reading RG6 6AJ, United Kingdom. E-mail p.d.weinberg{at}reading.ac.uk.

Abstract Uptake of circulating albumin by the aortic wall is greater downstream than upstream of branches in immature rabbits, but the opposite pattern occurs in mature animals. We investigated the role of NO in determining these variations. Descending thoracic aortas of rabbits were cannulated using techniques that avoid depressurization, overstretching, and excessive fluid dynamic stresses at the endothelial surface. They were perfused in situ at a constant pressure and flow rate with oxygenated, protein-containing physiological buffer, with or without N-monomethyl-L-arginine, an inhibitor of NO synthesis. Aortas were fixed 7 to 8 minutes after the addition of rhodamine-labeled albumin to this perfusate, and uptake of the tracer near intercostal ostia was measured by digital imaging fluorescence microscopy of sections through the wall. Despite the absence of pulsatile flow, blood cells, and many plasma components, patterns of transport in control experiments were the same as those occurring in vivo; uptake was greatest downstream of ostia in immature vessels and upstream in mature ones, although mean uptake was higher than previously reported. In the presence of the inhibitor, mean uptake in immature arteries was elevated threefold and the maximum tracer concentration occurred deeper in the wall, but there was no change in the fractional difference between regions. Conversely, the reverse of the control pattern of transport was observed in mature arteries exposed to the inhibitor, but there was no change in mean uptake. The reversal was almost entirely prevented by adding excess L-arginine to the perfusate and was largely stereospecific. Endogenous NO thus appears to determine the mature pattern of transport near branches and helps to maintain the barrier function of the immature wall.

Key Words: age • arterial branches • arterial permeability • endothelium-derived relaxing factor • nitric oxide

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