Are contraction and adhesion activated simultaneously by Angiotensin II in vascular smooth muscle?

Abstract

Administration of angiotensin (AII) at 10-7 M induces a rapid vasoconstrictor response. We propose that vascular smooth muscle cell (VSMC) contraction in response to AII is accompanied by changes in adhesion to the extracellular matrix (ECM). We hypothesized that integrin mediated ECM adhesion would be altered during AII mediated VSMC contraction. Initial whole cell adhesion studies, using a cell adhesion assay, demonstrated no appreciable difference in cell adhesion following 5–60 min AII treatment. However, studies were repeated using atomic force microscopy (AFM), which provides high temporal resolution and sensitivity for adhesion force detection. Low (p3~p4) and late passage (p7~p11) VSMCs isolated from 100–150 um diameter skeletal muscle arterioles were studied. AFM cantilever tips coated with fibronectin (FN) were allowed to interact with the cell surface for an initial 30 min control recording, and an additional 30–60 min following application of 10-7 M AII. AII induced a marked increase in VSMC elasticity, after 30 min treatment. The increase in cellular elasticity was preceded by an initial rapid (sec) change in cell shape (i.e. early contractile event). Adhesion data indicated an increase in average force and number of adhesion events, post AII. Our results suggest that integrin mediated adhesion changes occur during the mechanical response of VSMC to AII. (NIH R01HL102472 and P01HL095486)