Increase in endothelial cell density before artery enlargement in flow-loaded canine carotid artery

To investigate the morphologic basis of blood flow-dependent adaptive vascular enlargement, we quantitated endothelial cell density, dimensions, and structure in canine carotid arteries that were flow-loaded for 4 weeks, i.e., just before the development of significant adaptive enlargement. Increased flow was produced in the right common carotid artery of seven adult beagle dogs by an arteriovenous shunt to the right external jugular vein. The left common carotid artery was used to produce sham-operated controls. Five additional animals were used to produce sham-shunted controls, and two dogs were used as nonoperated controls. The blood flow rate (BFR) and wall shear rate (WSR) were markedly increased immediately after anastomosis in the proximal segment of the shunted artery (BFR = 719 +/- 142 ml/min, WSR greater than 4127 +/- 1002/sec) and after 4 weeks (BFR = 628 +/- 157 ml/min, WSR greater than 2919 +/- 388/sec) compared to the same artery before anastomosis (BFR = 154 +/- 50 ml/min, WSR = 904 +/- 314/sec, p less than 0.01 x 10(-3) for both comparisons) and to the contralateral control artery after 4 weeks (BFR = 365 +/- 110 ml/min, WSR = 2136 +/- 876/sec, p less than 0.01 and p less than 0.05, respectively, compared to the shunted side). In the shunted artery, endothelial cell density was markedly increased (6.15 +/- 0.68 x 10(3) cells/mm2 compared to 3.33 +/- 0.70 x 10(3) cells/mm2 for the controls, p less than 0.001). Endothelial cells on the high flow side were markedly narrowed in both axial and circumferential directions, but were radially thickened; nuclei became prolate-spheroid in shape. On the control side, cells were relatively flat and thin. We conclude that elevated wall shear stress induces an early increase in endothelial cell number and that this increase precedes the development of significant blood flow-dependent vascular enlargement.