Regulation of vasomotor tone by the cytoskeletal axis /

The cytoskeleton is an important structural component of all eukaryotic cells. While is has been know for some time that the cytoskeleton was responsible for the mechanical processes of locomotion, cell shape, contraction and division, more recent evidence has shown that cytoskeletal proteins can a...

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Bibliographic Details
Main Author: Platts, Steven Howard, 1965-
Format: Thesis Book
Language:English
Published: [Place of publication not identified] : [publisher not identified] ; 2000.
Subjects:
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Summary:The cytoskeleton is an important structural component of all eukaryotic cells. While is has been know for some time that the cytoskeleton was responsible for the mechanical processes of locomotion, cell shape, contraction and division, more recent evidence has shown that cytoskeletal proteins can and do transduce complex chemical signals as well. My main interest is in the role of the cytoskeletal axis in the regulation of vasomotor tone. This dissertation will focus on the physiological role of microtubules and actin containing microfilaments. Both of these cytoskeletal structures have been shown to affect cellular contractile function in a variety of cell types. My overall hypothesis is that remodeling of cytoskeletal elements plays an active role in the regulation/modulation of vascular smooth muscle contractile function, and thus vasomotor tone. Our lab has previously shown that integrin adhesion receptors (associated with the membrane attachment of the actin cytoskeleton) cause vasodilation when bound to RGD peptides chapter II consists of pharmacological studies using isolated arteriole preparations to investigate the mechanism of this response. Here we showed that K[] channels are activated by integrin-ligand binding. In chapter III the goal was to determine if altering the polymerization state of microtubules changes the contractile function of VSM and thus vasomotor tone. Colchicine, colcmid, and nocodazole were used to disrupt microtubules in isolated arterioles. All three microtubule depolymerizing agents produced increased vasomotor tone in a endothelium- and Ca[]-independent manner. Finally, we investigated the mechanism by which microtubule disruption increasees vasomotor tone. In chapter IV demecolcine and vinblastine were used in isolated arterioles in conjunction with agonists known to cause vasodilation through different signaling pathways. Additionally, a camp assay utilizing cultured smooth muscle cells was used to support the vascular studies. We concluded that modulation of the adenylate cyclase-cAMP pathway was not responsible for increased vasomotor tone, but more experiments are required to elucidate the signaling pathway responsible.
Item Description:Vita.
"Major Subject: Medical Science".
Physical Description:x, 98 leaves : illustrations ; 28 cm.
Issued also on microfiche from University Microfilm Inc.
Bibliography:Includes bibliographical references (leaves 88-96).