Roles of MEK/ERK Pathway in Vascular and Renal Tubular Actions of Angiotensin II

Chronic kidney disease (CKD) is now widely recognized as a significant risk factor for cardiovascular disease (CVD). Chronic angiotensin II (Ang II) stimulation facilitates tissue hyperplasia, hypertrophy, and inflammation, and the current medical strategy for CKD is primarily based on the suppression of rein-angiotensin system. Since Ang II induces hypertension through both vasoconstriction and sodium retention, the understanding of vascular and renal actions of Ang II is essential for the better management of CKD and CVD. Ang II is coupled to a variety of intracellular signaling pathways depending on cell types, and Ang II type 1 receptor (AT1) is thought to be responsible for most, if not all, of the cardiovascular effects of Ang II. Recent studies have suggested that the MEK/ERK pathway plays an important role in Ang II-mediated vascular smooth muscle contraction, where cytosolic phospholipase A2 (cPLA2)/P450 pathway has a positive feedback effect. Interestingly, the MEK/ERK pathway has been also shown to mediate the stimulatory effect of Ang II on renal proximal transport. However, the cPLA2/P450 pathway has a negative feedback effect on the Ang II-mediated ERK activation in renal proximal tubules. Thus, arachidonic acid metabolites seem to play quite contrasting roles in the Ang IImediated ERK activation in vascular and renal tissues. This article will be focused on the roles of MEK/ERK pathway in vascular and renal tubular actions of Ang II.