Influence of microtubules on vascular smooth muscle contraction

Microtubules are ubiquitous in eukaryotic cells and play key roles in many cellular activities. The purpose of this study was to investigate the influ ence of microtubules on vascular smooth muscle contraction. Quantitative im munocytochemical analysis of rat aortic tissue revealed that, relative to t he control group, colchicine (15 mu M, 90 min) and nocodazole (15 mu M, 90 min) decreased the microtubule density by 40-50% while taxol (10 mu M, 90 m in) increased the microtubule density by 33%. Isometric contraction studies demonstrated that both colchicine and nocodazole caused an upward shift in the phenylephrine (10(-8) to 10(-5) M) dose-response curve while taxol cau sed no significant change when compared to the control group. Potassium chl oride (30 mM) induced 55 +/- 5% P-0 contraction in DMSO treated vessel ring s. The active tension increased to 73 +/- 5% P-0 and 71 +/- 6% P-0 after pr etreatment of the aortic rings with colchicine or nocodazole, respectively. Taxol did not cause a significant change in the active tension (56 +/- 7% P-0). These results indicate that microtubule depolymerization enhances iso metric contraction of vascular smooth muscle and this enhanced contraction is not receptor dependent. Pretreatment of the aortic rings with an inhibit or of nitric oxide synthase (NOS) (N-omega-nitro-L-arginine) did not change the increased contractile response to phenylephrine due to microtubule dep olymerization suggesting that this phenomenon is not mediated by endotheliu m dependent relaxation.