The effect of high perfusion rates on the endothelial diffusion barrier in rat mesenteric arteries in vitro

1. Arteries from Wistar-Kyoto rat mesenteries were cannulated with glass cannulae and perfused with Krebs' solution at controlled rates and distending pressure. Arterial diameter was measured and concentration-response curves generated with agonists applied via the perfusate (luminal) and via the solution bathing the outside of the preparation (extraluminal). 2. The alpha 1-adrenoceptor selective agonist methoxamine was about three times more potent when applied extraluminally than intraluminally in arteries perfused at either 25 or 500 microL/min, but the lipophilic alpha 1-adrenoceptor selective agonist SKF 89748-A was equally potent with either mode of application. 3. The extraluminal/intraluminal potency differentials for both methoxamine and noradrenaline were abolished by perfusion for 30 min at a rate calculated to give a high shear stress (100 dyn/cm2). 4. The potency of luminally applied acetylcholine was reduced less than two-fold by the high shear perfusion, and the ability of acetylcholine to maximally relax the arteries was unchanged. 5. It is concluded that (i) the endothelium of small arteries reduces the potency of luminally applied lipophobic agonists by acting as a diffusion barrier; (ii) the ability of the endothelium to act as a diffusion barrier is easily damaged by shear stress in vitro; and (iii) the ability of acetylcholine to relax arteries in vitro is a poor index of the full functioning of the endothelium.