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 influence of microtubules on vascular smooth muscle contraction. Quantitative immunocytochemical analysis of rat aortic tissue revealed that, relative to the control group, colchicine (15 muM, 90 min) and nocodazole (15 muM, 90 min) decreased the microtubule density by 40-50% while taxol (10 muM, 90 min) 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 caused no significant change when compared to the control group. Potassium chloride (30 mM) induced 55 +/- 5% P0 contraction in DMSO treated vessel rings. The active tension increased to 73 +/- 5% P0 and 71 +/- 6% P0 after pretreatment of the aortic rings with colchicine or nocodazole, respectively. Taxol did not cause a significant change in the active tension (56 +/- 7% P0). These results indicate that microtubule depolymerization enhances isometric contraction of vascular smooth muscle and this enhanced contraction is not receptor dependent. Pretreatment of the aortic rings with an inhibitor of nitric oxide synthase (NOS) (Nomega-nitro-L-arginine) did not change the increased contractile response to phenylephrine due to microtubule depolymerization suggesting that this phenomenon is not mediated by endothelium dependent relaxation.
Zhang
D
D
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis 46202, USA.
Jin
N
N
Rhoades
R A
RA
Yancey
K W
KW
Swartz
D R
DR
D000818:Animals; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D019281:Dimerization; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D008297:Male; D008870:Microtubules / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology* / Q000648:ultrastructure; D015739:Nocodazole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D015739:Nocodazole; D003078:Colchicine; D004121:Dimethyl Sulfoxide