Shear Stress-Dependent Endothelial NO Release

The mechanism by which the endothelium is able to sense changes in shear on its luminal surface remains obscure, although there have been 

FIGURE I Histograms illustrating the effect of bradykinin (10 nM) on (A) intracellular pH (pHi), (B) the intracellular concentration of free calcium ([Ca ]j), and (C) the activation of soluble guanylate cyclase (SGC) by effluent from unstimulated (basal) and bradykinin (2 and 20 min) human umbilical vein endothelial cells. Experiments were performed in the absence (open bars) and the presence (hatched bars) of the Na /H exchange inhibitor HOE 694 (10 /LtM). Results are expressed as the means SEM of data obtained using seven different cell batches. , P 0.05 , P 0.01. 

1991) and in vitro (Franke et al., 1984 Wechezak et al., 1985) and alters the topography of endothelial cells such that they become streamlined in the direction of flow (for a review see Davies and Tripathi, 1993). Other shear-induced effects, such as the increase in endothelin-1 mRNA levels, can be mimicked by the actin-disrupting agents cytochalasin B and D and 

The intracellular signal transduction pathway that is initiated by increases in shear stress has been reported to involve activation of phospholipase C (Bhagyalakshmi et al., 1992) and a rapid increase in intracellular levels of inositol 1,4,5-trisphosphate (Nollert et al., 1990 Prasad et al., 

enhanced release of NO (Rubanyi et al., 1986 Pohl et al., 1986), and increased cellular levels of cGMP (Ohno et al., 1993). Induction of some early-response genes can be detected shortly after application of shear (e.g., c-myc after several minutes and c-fos and c-jun within 2 hr) (Ranjan and Diamond, 1993), as well as activation of the transcription factors AP-1 and NF-kB (Lan et al., 1994). 

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