-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...