Aquaporin-1 facilitates pressure-driven water flow across the aortic endothelium

Abstract

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.

The water channel AQP1 is expressed in human atherosclerotic vascular lesions and AQP1 deficiency augments angiotensin II‐induced atherosclerosis in mice

“…In the endothelial layer of these arteries, AQP1 sets the critical transmural pressure for subendothelial intima compression (Nguyen et al . ) and may regulate solute advection like low‐density lipoprotein cholesterol (LDL) (Tedgui & Lever ). LDL entry to the subendothelial intima layer is one of the early steps in atherogenesis (Simionescu et al .…”

Direct visualization of the arterial wall water permeability barrier using CARS microscopy

“…Many have suggested that the major barrier to water permeability is the endothelial cell (EC) layer based on the effect of gross mechanical disruption of these cells (1,10,12). Recent data have shown that inhibition of AQP1, highly expressed in vascular EC (13), has little impact on the measured water permeability at physiological pressures (14), suggesting that AQP1-facilitated water transport across the endothelium is not rate limiting. In this study we characterize the distribution of permeability and the associated pressure profile across the wall, in in vitro intact pressurized rat mesenteric arteries.…”

A novel method for measuring hydraulic conductivity at the human blood-nerve barrier in vitro

“…Further studies are required to determine the effect of GDNF and other mitogens such as basic fibroblast growth factor, transforming growth factor-β, vascular endothelial growth factor and hydrocortisone on BNB water flux. It is currently unknown whether hydraulic conductivity at the BNB or BBB is facilitated by specific water channels (such as aquaporin 1) (Nguyen et al, 2015) providing a transcellular route of entry or via transcellular or paracellular osmosis. In future studies, gene knock-down could be employed to manipulate tight junction, transporter, and ionic/water channel protein levels using pHEndECs or THEndECs, or THBMECs to gain insights to their roles in BNB and BBB hydraulic conductivity respectively.…”