Disruption of microtubular network attenuates histamine-induced dilation in rat mesenteric vessels.
Cytoplasmic microtubules are important in many cellular homeostatic processes in the cell. They regulate cell shape and movement as well as serving as a network by which vesicles and membrane-bound organelles can travel. Lately, there have been many studies demonstrating that microtubules are involved in regulation of intracellular signaling and, therefore, affect vascular reactivity. In this study, we tested the hypothesis that microtubule disruption attenuates agonist-induced endothelium-dependent vasodilation. Isolated mesenteric arterial bed from normotensive rats was preconstricted with phenylephrine, and dose-response curves for histamine, acetylcholine (ACh), sodium nitroprusside (SNP), and pinacidil were performed before and after incubation with nocodazole or colchicine. Treatment of the vascular beds with nocodazole or colchicine significantly attenuated histamine relaxation but did not change the ACh-, SNP-, or pinacidil-induced vasorelaxation. Nocodazole did not cause an additional attenuation of the histamine-mediated dilation in mesenteric vessels in the presence of Nomega-nitro-L-arginine methyl ester, high extracellular K+, or K+ channel blockers. These data suggest that disruption of microtubules affects an essential endothelial component of histamine-mediated vasodilation in the mesenteric arterial bed. The mechanism(s) involved in this effect might be related to an impairment of endothelial NO synthesis, which might not be as important for the ACh as for the histamine vasodilator response in rat mesenteric vessels. These results demonstrate the importance of the microtubular system for endothelium-dependent NO-mediated smooth muscle relaxation.
Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912-3000, USA.
Carla de Arêdes
Cde A
Brum
Igor Dimitri Gama
ID
Duarte
R Clinton
RC
Webb
Romulo
R
Leite
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006074:Gout Suppressants / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000970:Antineoplastic Agents; D006074:Gout Suppressants; D014665:Vasodilator Agents; D009569:Nitric Oxide; D006632:Histamine; D015739:Nocodazole; D003078:Colchicine