Regulation of capillary hydraulic conductivity in response to an acute change in shear

Abstract

-The effects of mechanical perturbations (shear stress, pressure) on microvascular permeability primarily have been examined in micropipette-cannulated vessels or in endothelial monolayers in vitro. The objective of this study is to determine whether acute changes in blood flow shear stress might influence measurements of hydraulic conductivity (Lp) in autoperfused microvessels in vivo. Rat mesenteric microvessels were observed via intravital microscopy. Occlusion of a third-order arteriole with a micropipette was used to divert and increase flow through a nonoccluded capillary or fourth-order arteriolar branch. Using the micropipette occlusion technique in autoperfused rather than cannulated capillaries, Landis described how the fluid filtration rate was most rapid in the initial seconds following occlusion, becoming significantly slower in less than 1 min. This was attributed at least in part to the possibility that plasma oncotic pressure could increase with time in an occluded vessel as a result of greater efflux of water than of protein. However, another consideration is that the vessel occlusion includes an abrupt change in flow-induced shear stress and pressure, both of which could have a time-dependent effect on L p .As a microvessel is occluded, blood flow decreases from its basal value to essentially zero. Several studies have shown that transvascular exchange can be affected by a change in perfusion rate (14,17,19,32,33,43). A small-pore model has been proposed as a possible mechanism to account for flow-dependent transport of small solutes in cannulated vessels (32); moreover, there have been several recent studies of shearinduced increases in fluid filtration performed in vitro (3, 6, 37) and in vivo (27,40,41). The mechanism by which shear forces could increase L p appear to be dependent on nitric oxide (NO) (3,15,24). Therefore, when a capillary stops flowing, it might be expected that L p could decline in a matter of seconds as shear-induced production of NO is attenuated.Another mechanical factor associated with microvessel occlusion is the step increase in hydrostatic pressure. For example, when a capillary is occluded at its downstream end, pressure throughout the vessel increases to that of the feeding arteriole. Recent studies (7,38) indicate that a step increase in hydrostatic pressure causes a decrease in L p in what has been called a "sealing effect." However, the time courses of the changes in L p in these studies were over a period of minutes to hours.The effects of shear on L p have been examined previously in micropipette-cannulated vessels or in endothelial monolayers in vitro. The primary objective of the current study was to determine whether acute changes in blood flow shear might influence measurements of L p in autoperfused, rather than cannulated, microvessels. In addition, a role for NO in shearmediated changes in L p was investigated. MATERIALS AND METHODSAnimal preparation. Animal procedures were approved by an Institutional Animal Care And Use Committee. Male Wistar rats ϳ2...

Change in shear stress (Δτ)/hydraulic conductivity (Lp) relationship after pronase treatment of individual capillaries in situ

“…In situ studies indicate that capillary L p correlates with relative change in τ in mesenteric capillaries of frog (Williams, 1999) and rat (Kim et al, 2005). Consistent with the culture and capillary data are reports from whole organ preparations where permeability to surface area product increased with changes in flow (Rippe et al, 1978), red blood velocity in skeletal muscle capillaries correlated with permeability to Cr-EDTA (Shibata and Kamiya, 1992), and capillary filtration coefficient rose rapidly with exercise (Björnberg, 1990).…”

Flow shear stress regulates endothelial barrier function and expression of angiogenic factors in a 3D microfluidic tumor vascular model

“…These findings are consistent with others showing shear stress-mediated endothelial morphological adaptations 22,38,[49][50][51][52] and permeability. 14,17,19,21,23,53 The presence of tumor cells also increased P d relative to endothelial mono-cultures, with a significantly greater P d under high WSS conditions. Images taken at the end of the permeability assay for the case of t W D 10 dyn/ cm 2 qualitatively show greater distribution of dextran across the endothelium during co-culture with tumor cells, relative to dextran distribution immediately post 72 hrs preconditioning (Fig.…”

“…Many reports have documented the effect of wall shear stress (WSS) on endothelial cell-matrix interactions, junction molecules, gene expression, barrier transport properties, and angiogenesis. [14][15][16][17][18][19][20][21][22][23][24][25][26][27] For example, reports have shown that shear stress causes upregulation of Tie2 and MMP-1 25 and increases vascular endothelial growth factor (VEGF) expression in endothelial cells. 28 Similar studies have also shown that shear stress stimulates endothelial cell migration as well as supports blood vessel maintenance.…”

Age-Related Changes in Carotid Artery Flow and Pressure Pulses

“…37,38 The enhanced permeability in small vessels has been reported as a manifestation of damage to small vessels in the brain and has been proposed as an important pathogenesis of cerebral microvascular disease. 39,40 Our analysis of components of the carotid artery flow waveform only supports the aforementioned view.…”