Microtubule disruption modulates the Rho-kinase pathway in vascular smoothmuscle

Microtubules constitute one of the main cytoskeletal components in eukaryot ic cells. Recent studies have shown that microtubule disruption induced sig nificant vasoconstriction or enhanced agonist-induced contraction in vascul ar smooth muscle. However, the underlying mechanisms are not clear. We hypo thesize that microtubule disruption may affect contractile signaling in vas cular smooth muscle and lead to the enhanced contraction. The present study demonstrates that both colchicine and nocodazole induced a small but susta ined contraction (4-6% P-0) in rat aortic rings. This microtubule disruptio n-induced contraction was abolished by co-treatment with either HA 1077 or Y-27632, both of which are relatively specific Rho-kinase inhibitors. Howev er, co-treatment with ML-9, an inhibitor of myosin light chain kinase, (MLC K) did not have a significant effect on the colchicine-induced contraction. The enhanced KCl-induced contraction due to treatment with colchicine was also blocked by inhibition of Rho-kinase, but not by inhibition of MLCK. Th ese results indicate that microtubule disruption modulates contractile sign aling in vascular smooth muscle, mainly through the Rho-kinase pathway, but not MLCK. Interestingly, the colchicine-enhanced, phenylephrine-induced co ntraction was not completely blocked by inhibition of Rho-kinase suggesting that other signaling pathways might also be involved.