Mechanotransduction through the endothelial cytoskeleton: mediation of flow‐ but not agonist‐induced EDRF release

• Published in: British journal of pharmacology Vol. 118; no. 3; pp. 720 - 726
• Main Authors: Hutcheson, Iain R., Griffith, Tudor M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.1996; Nature Publishing
• Subjects: Acetylcholine - pharmacology; Actin Cytoskeleton - physiology; Animals; Aorta - drug effects; Biological and medical sciences; Blood vessels and receptors; cytoskeleton; Cytoskeleton - metabolism; endothelium‐derived relaxing factor (EDRF); Fundamental and applied biological sciences. Psychology; Male; Nitric Oxide - metabolism; Nitroprusside - pharmacology; Rabbit aorta; Rabbits; Space life sciences; time‐averaged shear stress; Vertebrates: cardiovascular system; Viscosity; Actins; Rabbit; Microfilament; Lagomorpha; In vitro; Endothelium; Abdominal aorta; Vertebrata; Vasomotricity; Mammalia; Tubulin; Animal; Blood vessel; Cytoskeleton; Endothelium derived relaxing factor; Microtubule
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1996.tb15459.x

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 μm) 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 μm) 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 μm) 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.