Crucial role of endothelium in the vasodilator response to increased flow in vivo.

TLDR

The study aimed to determine how vascular endothelium contributes to flow‑dependent dilation in conduit arteries. Using sonomicrometry in 23 anesthetized dogs, the authors measured femoral artery diameter changes during flow increases, before and after endothelial damage, and assessed endothelial integrity with intra‑arterial acetylcholine. Flow augmentation caused dilation in most dogs, but endothelial removal or oxidative damage eliminated flow‑dependent and acetylcholine dilation while preserving norepinephrine and nitroglycerin responses, indicating endothelial cells mediate flow‑dependent dilation.

Abstract

Experiments were designed to investigate the importance of vascular endothelium in the vasomotor response to increases in flow as observed in conduit arteries (flow-dependent dilation). The diameter changes of femoral arteries (sonomicrometry) in response to increases in flow before and after endothelial damage procedures were studied in 23 dogs anesthetized with sodium pentobarbital. The functional integrity of the endothelial cells underneath the diameter sensors was tested by intra-arterial acetylcholine (local acetylcholine dilation) applied proximally to the sensors while a constant flow was maintained. Unilateral augmentation of femoral arterial flow (4.6 +/- 1.9-fold) induced by peripheral vasodilation or by arteriovenous shunt, elicited dilation (increase in diameter, 116 +/- 91 microns) in 18 of 23 dogs, whereas the diameter of the contralateral control artery was not affected. Mechanical removal of the endothelial cells by means of a balloon catheter abolished both the flow-dependent dilation and the local acetylcholine dilation, whereas the vasomotor responses to norepinephrine and nitroglycerin were not affected. Brief perfusions (1 minute) of the arteries with cell-free hydrogen peroxide solution (90 mM) also abolished the flow-dependent dilation and attenuated the local acetylcholine dilation (by 27 +/- 19%; p less than 0.02), while the responses to norepinephrine and nitroglycerin were not altered. These results suggest that endothelial cells act as mediators of flow-dependent dilation.