Alteration of microtubule polymerization modulates arteriolar vasomotor tone

Abstract

Microtubules are important cytoskeletal elements that have been shown to play a major role in many cellular processes because of their mechanical properties and/or their participation in various cell signaling pathways. We tested the hypothesis that depolymerization of microtubules would alter vascular smooth muscle (VSM) tone and hence contractile function. In our studies, isolated cremaster arterioles exhibited significant vasoconstriction that developed over a 20- to 40-min period when they were treated with microtubule depolymerizing drugs colchicine (10 μM), nocodazole (10 μM), or demecolcine (10 μM). Immunofluorescent labeling of microtubules in cultured rat VSM revealed that both colchicine and nocodazole caused microtubule depolymerization over a similar time course. The vasoconstriction was maintained over a wide range of intraluminal pressures (30–170 cmH2O). The increased tone was not affected by endothelial denudation, suggesting that it was due to an effect on VSM. Microtubule depolymerization with demecolcine or colchicine had no effect on VSM intracellular Ca2+ concentration ([Ca2+]i). These data indicate that microtubules significantly interact with processes leading to the expression of vasomotor tone. The mechanism responsible for the effect of microtubules on vasomotor tone appears to be independent of both the endothelium and an increase in VSM [Ca2+]i.

Control of Myofibroblast Differentiation by Microtubule Dynamics through a Regulated Localization of mDia2

“…4B) or 24 h (Fig. 4C) redistributed tubulin to the insoluble and soluble fractions, respectively, which is consistent with previously published observations (23). Despite the lack of effect TGF-␤ on microtubule dynamics, stabilization of microtubules by paclitaxel resulted in inhibition of TGF-␤1-induced expression of myofibroblast-associated genes, including ␣-SMA, CTGF, and SRF, both at mRNA and protein levels (Fig.…”

“…Microtubule Disruption Promotes Myofibroblast Differentiation in a Rho/SRF-dependent, Smad-independent Manner-To examine whether microtubule polymerization state could influence fibroblast morphology and differentiation, we first utilized the direct pharmacologic inhibitor of microtubule polymerization, colchicine, which has been shown to fully depolymerize microtubules after 60 min (23). Treatment of human lung fibroblasts (HLF) with colchicine for 24 h resulted in a significant decrease in microtubule staining (Fig.…”

Delayed arteriolar relaxation after prolonged agonist exposure: functional remodeling involving tyrosine phosphorylation

“…Previous studies in our laboratories (37) showed modulation of arteriolar contractile responses to NE by the polymerization state of the microtubular network. Therefore, to examine the possible involvement of the microtubular network in the differ-ences in contractile responses to acute and prolonged NE exposure, experiments were performed in the absence and presence of the depolymerizing agent demecolcine (10 M).…”

“…The prolonged response (4 h) to NE was then determined in the continued presence of demecolcine. Conditions for these experiments were established in previous studies (37,38).…”

The Plastic Nature of the Vascular Wall: A Continuum of Remodeling Events Contributing to Control of Arteriolar Diameter and Structure

“…PHYSIOLOGY (162), whereas for microtubules it has been shown that tubular disruption induces vasoconstriction and augments vascular responsiveness to adrenergic stimulation via calcium sensitization processes dependent on the Rho kinase pathway (41, 130,131). However, the overall roles of intermediate filaments or the microtubules on the regulation of contractile function in vascular smooth muscle cells leading to control of vascular diameter is poorly understood and requires further investigation.…”