Key points are not available for this paper at this time.
We have used a cascade bioassay system and isolated arterial ring preparations to investigate the contribution of the endothelial microfilament and microtubule cytoskeleton to EDRF release evoked by time‐averaged shear stress and by acetylcholine in rabbit abdominal aorta. Cytochalasin B (1 μ m ) and phalloidin (100 nM) were used to depolymerize and stabilize, respectively, F‐actin microfilaments. Colchicine (500 nM) was used to inhibit tubulin dimerization and thus disrupt the microtubule network. Experiments were performed before or 1 h after administration of agents to the donor perfusate or organ bath. In cascade bioassay studies, time‐averaged shear stress was manipulated with dextran (1–4% w/v, 80,000 MW), to increase perfusate viscosity. EDRF release induced by increased perfusate viscosity was significantly ( P < 0.01) attenuated by cytochalasin B, phalloidin and colchicine. Endothelium‐dependent relaxations to acetylcholine (0.01–30 μ m ) in cascade bioassay and in isolated aortic ring preparations were unaffected by pretreatment with any of these agents both in terms of their EC 50 and maximal responses. Endothelium‐independent relaxations to sodium nitroprusside (0.001–10 μ m ) were similarly unaffected. We conclude that the endothelial F‐actin microfilament and microtubule networks are involved in the mechanotransduction pathway for flow‐evoked EDRF release in rabbit abdominal aorta. However, these cytoskeletal elements appear to play no role in acetylcholine‐induced EDRF release in this tissue.
Hutcheson et al. (Sat,) studied this question.