Dissertation/Thesis Abstract

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Contribution of AT1R Mechanoactivation to the Arterial Myogenic Response and Its Regulation by RGS5 Protein in Skeletal Muscle Arterioles
by Hong, Kwangseok, Ph.D., University of Missouri - Columbia, 2015, 239; 13869878
Abstract (Summary)

Although intracellular mechanisms underlying the arteriolar myogenic response have been well-defined, the mechanotransduction events transducing the mechanical stimulus remain unclear. Recently, ligand-independent activation of G protein-coupled receptors (in particular, the angiotensin II type 1 receptor; AT1R) has been suggested to play a major role in vascular smooth muscle mechanotransduction, thereby contributing to myogenic constriction. However, the downstream pathways following ligandindependent activation of the AT1R have not been clearly elucidated. Our studies provide pharmacological evidence that the mechanically activated AT1R generates diacylglycerol which in turn activates PKC that subsequently induces actin cytoskeleton reorganization for myogenic constriction. In terms of physiological roles, the arterial myogenic response acts to generate vascular tone, prevent capillaries from being damaged, and reduce edema due to high capillary hydrostatic pressure. Thus, an exaggerated AT1R-mediated myogenic constriction could conceivably contribute to vascular disorders. As a result, small arteries likely exhibit negative feedback regulatory mechanisms to prevent such an exaggerated myogenic response. In regard to this, we discovered that ligand-dependent or -independent activation of the AT1R causes trafficking of an important regulatory molecule, RGS5 (Regulators of G protein Signaling) protein, which may modulate Ang II or myogenic-mediated constriction by terminating Gq/11 protein-dependent signaling.

Indexing (document details)
Advisor: Hill, Michael A.
Commitee: Davis, Michael J., Hill, Michael A., Laughlin, M. Harold, Meininger, Gerald A.
School: University of Missouri - Columbia
Department: Medical Pharmacology and Physiology
School Location: United States -- Missouri
Source: DAI-B 80/08(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Health sciences, Physiology
Keywords: Mechanotransduction, Myogenic response, Regulators of G protein signaling proteins, Skeletal muscle arterioles
Publication Number: 13869878
ISBN: 9781392012307
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