Comparison of Receptor Efficacies on Vascular Smooth Muscle Contraction

<p>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 (AT₁agonist), 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 AT₁and 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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Physiology

Year

2003

Author dc:creator

• George, Oommen K.

Contributors dc:contributor

• Ramon R. Gonzalez, Jr
• Lincoln P. Edwards
• Raymond G. Hall, Jr.
• George T. Javor
• Robert W. Teel

• Physiology
• Muscle, Smooth -- drug effects -- dissertations; Receptors, Angiotensin -- metabolism; Vasoconstrictor Agents -- pharmacology.

Statement dc:rights

• This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/856

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-2002