MONOCYTE ADHESION AND CHANGES IN ENDOTHELIAL-CELL NUMBER, MORPHOLOGY,AND F-ACTIN DISTRIBUTION ELICITED BY LOW SHEAR-STRESS INVIVO

Left common carotid arteries of New Zealand white rabbits were ligated rostral to origin of the thyroid artery to reduce flow in the carotid upstream of this branch, and the vessels were examined 5 days later. Estimates of mean shear stress in the upstream carotid artery indicate d a decrease of 73% (from 12.1 +/- 1.6 dynes/cm2 to 3.26 +/- 0.58 dyne s/cm2). The contralateral common carotid artery carried collateral flo w and experienced a 170% increase in shear stress (from 11.3 +/- 1.6 d ynes/cm2 to 30.5 +/- 4.6 dynes/cm2). There was an adaptive reduction i n the diameter in the left common carotid artery (low shear) from 2.07 +/- 0.06 mm to 1.75 +/- 0.12 mm, but the diameter of the right caroti d was unchanged. Fluorescence microscopy and scanning electron microsc opy of endothelium exposed to low shear revealed attachment of leukocy tes (5.02 +/- 1.59 cells/mm2, mean +/- SE) that were identified as mon ocytes using the monoclonal antibody HAM 56 Laser confocal microscopy demonstrated that they were migrating across the endothelial cell mono layer. Fluorescence microscopy and scanning electron microscopy of lef t common carotid artery (low shear) also revealed cell morphology sugg estive of endothelial cell desquamation. Endothelial cell loss was con firmed by morphometric determination of cell number (1.29 +/- 0.13 X 1 0(4) cells/mm length in experimental animals versus 1.71 +/- 0.08 X 10 (4) cells/mm length in sham-operated animals). This endothelial cell l oss may be an adaptation to a narrowing of carotid arteries exposed to low shear, which reduces luminal surface area of the vessel Staining of F-actin with rhodamine phalloidin showed that endothelial cells exp osed to low shear were less elongated and had fewer stress fibers than normal cells. By contrast, increasing shear stress by two- to threefo ld caused an increase in the number of stress fibers and a reduction i n peripheral actin staining. Distal carotid ligation provided a consis tent and well-defined in vivo technique for manipulating shear stresse s imposed on a large population of endothelial cells.