Comparison of Receptor Efficacies on Vascular Smooth Muscle Contraction

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