Alteration of microtubule polymerization modulates arteriolar vasomotor tone

Microtubules are important cytoskeletal elements that have been shown to pl ay a major role in many cellular processes because of their mechanical prop erties and/or their participation in various cell signaling pathways. We te sted the hypothesis that depolymerization of microtubules would alter vascu lar 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 microtub ule depolymerizing drugs colchicine (10 mu M), nocodazole (10 mu M), or dem ecolcine (10 mu M). Immunofluorescent labeling of microtubules in cultured rat VSM revealed that both colchicine and nocodazole caused microtubule dep olymerization over a similar time course. The vasoconstriction was maintain ed over a wide range of intraluminal pressures (30-170 cmH(2)O). The increa sed 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 proces ses 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).