Vascular smooth muscle contraction involves multiple signal-transduction pathways, the interrelations of which are not completely understood. Our objectives in this project were to compare the effects of phenylephrine (alpha1-adrenergic agonist, angiotensin II (AT1 agonist), clonidine (alpha2-adrenergic agonist) and moxondine (alpha2- adrenergic /I1-imidazoline agonist) on contraction in the rat-tail artery. Functionally, all these agonists cause contraction, but biochemically there are differences in how the result is achieved. We wanted to determine the role of protein kinase C (PKC) in the functional regulation between AT1 and alpha1-adrenergic receptor pathways. In addition, we were interested in elucidating the effects of moxonidine on the rat-tail artery. Our study demonstrates that the alpha1-adrenergic receptor is the major receptor for mediating contraction in the rat-tail artery. The postsynaptic alpha2-adrenergic receptor also plays a significant role in rat-tail artery contraction, but to a lesser extent than the alpha1-adrenergic receptors. Similarly, AT1 receptors are involved in rat-tail artery contraction, but to a lesser extent than the adrenergic receptors. I1 receptors were not found in rat-tail artery contraction. The data also suggest that PKC plays a greater role in the contractile response mediated by AT1 receptor than the alpha1-adrenergic receptor. The AT1 receptor response seems to affect PLD, resulting in PKC effects downstream. We finally, show that moxonidine, a known I1/alpha2-adrenergic agonist, mediates rat-tail artery contraction via the activation of alpha2-and alpha1-adrenergic receptors, and not via specific imidazoline receptors.
Ramon R. Gonzalez, Jr
Lincoln P. Edwards
Raymond G. Hall, Jr.
George T. Javor
Robert W. Teel
Doctor of Philosophy (PhD)
Year Degree Awarded
Date (Title Page)
Library of Congress/MESH Subject Headings
Muscle, Smooth -- drug effects -- dissertations; Receptors, Angiotensin -- metabolism; Vasoconstrictor Agents -- pharmacology.
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George, Oommen K., "Comparison of Receptor Efficacies on Vascular Smooth Muscle Contraction" (2003). Loma Linda University Electronic Theses, Dissertations & Projects. 856.
Loma Linda University Electronic Theses and Dissertations
Loma Linda University. Del E. Webb Memorial Library. University Archives