Mechanotransduction through the endothelial cytoskeleton: mediation of flow- but not agonist-induced EDRF release.
1. 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. 2. Cytochalasin B (1 microM) 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. 3. 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. 4. Endothelium-dependent relaxations to acetylcholine (0.01-30 microM) in cascade bioassay and in isolated aortic ring preparations were unaffected by pretreatment with any of these agents both in terms of their EC50 and maximal responses. Endothelium-independent relaxations to sodium nitroprusside (0.001-10 microM) were similarly unaffected. 5. 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
I R
IR
Department of Diagnostic Radiology, University of Wales College of Medicine, Heath Park, Cardiff.
Griffith
T M
TM
D000109:Acetylcholine / Q000494:pharmacology*; D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D003599:Cytoskeleton / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D014783:Viscosity
D009599:Nitroprusside; D009569:Nitric Oxide; D000109:Acetylcholine