ERK activation by the alpha1‐adrenergic receptor agonist phenylephrine in human aortic smooth muscle (AoSMC) cells

Abstract

The adaptive process of vascular remodeling causes structural alteration in blood vessels via proliferation, differentiation and migration of vascular smooth muscle cells (VSMCs) within the vessel wall. These changes play roles in both normal vessel activity and the appearance of pathophysiological conditions such as hypertension and atherosclerosis. ERK plays a role in all of these activities, and α‐adrenergic receptors (αARs) activate ERK by classic second messengers and by EGF receptor (EGFR) transactivation. Using a phosphoantibody cell‐based ELISA, we measured ERK activation by α1 and α2AR agonists. While AoSMCs express both α1 and α2ARs, ERK was activated only by the α1 agonist phenylephrine (PE). Surprisingly, the α1 agonist cirazoline had no effect on ERK activity. ERK activation by PE was blocked by the α1 antagonist prazosin and the α1A antagonist SNAP 5089 but was not affected by the α1D antagonist BMY 7378. While EGFR downregulation reduced ERK activation by PE, the EGFR inhibitor PD168393 did not. Further study will be necessary to elucidate the exact role of the EGFR in PE‐mediated ERK activation; however, our data show that activation of ERK by PE occurs in a potentially EGFR‐dependent process via activation of α1A but not α1DARs. Ultimately, we wish to determine αAR subtype‐specific, ERK‐mediated expression of immediate early genes which play a role in the processes involved in vascular remodeling.