Aquaporin-1, a ubiquitous water channel membrane protein, is a major contributor to cell membrane osmotic water permeability. Arteries are the physiological system where hydrostatic dominates osmotic pressure differences. In the present study, we show that the walls of large conduit arteries constitute the first example where hydrostatic pressure drives aquaporin-1-mediated transcellular/transendothelial flow. We studied cultured aortic endothelial cell monolayers and excised whole aortas of male Sprague-Dawley rats with intact and inhibited aquaporin-1 activity and with normal and knocked down aquaporin-1 expression. We subjected these systems to transmural hydrostatic pressure differences at zero osmotic pressure differences. Impaired aquaporin-1 endothelia consistently showed reduced engineering flow metrics (transendothelial water flux and hydraulic conductivity). In vitro experiments with tracers that only cross the endothelium paracellularly showed that changes in junctional transport cannot explain these reductions. Percent reductions in whole aortic wall hydraulic conductivity with either chemical blocking or knockdown of aquaporin-1 differed at low and high transmural pressures. This observation highlights how aquaporin-1 expression likely directly influences aortic wall mechanics by changing the critical transmural pressure at which its sparse subendothelial intima compresses. Such compression increases transwall flow resistance. Our endothelial and historic erythrocyte membrane aquaporin density estimates were consistent. In conclusion, aquaporin-1 significantly contributes to hydrostatic pressure-driven water transport across aortic endothelial monolayers, both in culture and in whole rat aortas. This transport, and parallel junctional flow, can dilute solutes that entered the wall paracellularly or through endothelial monolayer disruptions. Lower atherogenic precursor solute concentrations may slow their intimal entrainment kinetics.

Shou, Yixin, Kung-ming Jan, and David S. Rumschitzki. Transport in rat vessel walls. I. Hydraulic conductivities of the aorta, pulmonary artery, and inferior vena cava with intact and denuded endothelia. Am J Physiol Heart Circ Physiol 291: H2758 -H2771, 2006. First published May 26, 2006 doi:10.1152/ajpheart.00610.2005In this study, filtration flows through the walls of the rat aorta, pulmonary artery (PA), and inferior vena cava (IVC), vessels with very different susceptibilities to atherosclerosis, were measured as a function of transmural pressure (⌬P), with intact and denuded endothelium on the same vessel. Aortic hydraulic conductivity (L p) is high at 60 mmHg, drops ϳ40% by 100 mmHg, and is pressure independent to 140 mmHg. The trends are similar in the PA and IVC, dropping 42% from 10 to 40 mmHg and flat to 100 mmHg (PA) and dropping 33% from 10 to 20 mmHg and essentially flat to 60 mmHg (IVC). Removal of the endothelium renders L p(⌬P) flat: it increases Lp of the aorta by ϳ75%, doubles L p of the PA, and quadruples Lp of the IVC. Specific resistance (1/L p) of the aortic endothelium is ϳ47% of total resistance; i.e., the endothelium accounts for ϳ47% of the ⌬P drop at 100 mmHg. The PA value is 55% at Ͼ40 mmHg, and the IVC value is 23% at 10 mmHg. L p of the intact aorta, PA, and IVC are order 10 Ϫ8 , 10 Ϫ7 , and 5 ϫ 10 Ϫ7 cm⅐s Ϫ1 ⅐mmHg Ϫ1, and wall thicknesses are 145.8 m (SD 9.3), 78.9 m (SD 3.3), and 66.1 m (SD 4.1), respectively. These data are consistent with the different wall structures of the three vessels. The rat aortic L p data are quantitatively consistent with rabbit Lp(⌬P) (Tedgui A and Lever MJ.

Transendothelial lipid transport into and spread in the subendothelial intima of large arteries, and subsequent lipid accumulation, appear to start plaque formation. We experimentally examine transendothelial horseradish peroxidase (HRP) transport in vessels that are usually, e.g., pulmonary artery (PA), or almost always, e.g., inferior vena cava (IVC), atherosclerosis resistant vs. disease prone, e.g., aorta, vessels. In these vessels, HRP traverses the endothelium at isolated, focal spots, rather than uniformly, for short circulation times. For femoral vein HRP introduction, PA spots have 30-s radii [ approximately 53.2 microm (SD 10.4); compare aorta: 54.6 microm (SD 8.75)] and grow quickly from 30 s to 1 min (40%, P<0.05) and more slowly afterward (P>0.05). This trend resembles the aorta, suggesting the PA has a similarly sparse intima. With carotid artery (CA) HRP introduction, the 30-s spot (132.86 +/- 37.32 microm) is far larger than the PAs, grows little ( approximately 28%, P<0.05) from 30 to 60 s, and is much flatter than the artery curves. Transverse electron microscopic sections after approximately 10 min HRP circulation show thin, intense staining immediately beneath both vessels' endothelia with an almost step change to diffuse staining beyond. This indicates the existence of a sparse, subendothelial intima, even when there is no internal elastic lamina (IVC). This motivates a simple model that translates growth rates into lower bounds for the flow through focal leaks. The model results and our earlier wall and medial hydraulic conductivity data explain these spot growth curves and point to differences in transport patterns that might be relevant in understanding the immunity of IVC to disease initiation.

Atherosclerosis is a disease mainly of large, high pressure arteries and of valves, typically sparing veins and small, low pressure arteries. We investigate the resistances of the vena cava and the pulmonary artery to the flow of water and the infiltration of solutes into the vessel walls and compare them with similar processes in the aorta. The goal is to see if differences in macromolecular transport from the blood into the vessel wall amongst vessels can explain their different susceptibilities to atherosclerosis.

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