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. 1996 Jun;118(3):720–726. doi: 10.1111/j.1476-5381.1996.tb15459.x

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

I R Hutcheson 1, T M Griffith 1
PMCID: PMC1909742  PMID: 8762099

Abstract

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.

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Selected References

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