Activation of resistance arteries with endothelin-1: From vasoconstriction to functional adaptation and remodeling

Abstract

Remodeling of resistance arteries is a key feature in hypertension. We studied the transition of vasoconstriction to remodeling in isolated rat skeletal muscle arterioles. Arterioles activated with 10 nM endothelin-1 showed functional adaptation when kept at low distension in a wire myograph setup, where contractile properties shifted towards a smaller lumen diameter after 1 day. Pressurized arteries kept in organoid culture showed physical inward remodeling after 3-day activation with 10 nM endothelin-1, characterized by a reduction in relaxed diameter without a change in the wall cross-sectional area (eutrophic remodeling). The relaxed lumen diameter (at 60 mm Hg) decreased from 169 ± 5 (day 0) to 155 ± 4 μm (day 3). An antibody directed to the β3-integrin subunit (but not one directed to the β1-integrin subunit) enhanced remodeling, from a reduction in relaxed diameter at 60 mm Hg of 15 ± 2.4 to 22 ± 1.8 μm (both on day 3). Collagen gel contraction experiments showed that the antibody directed to the β3-integrin subunit enhanced the compaction of collagen by smooth muscle cells, from 83 ± 1.5 to 68 ± 1.5% of the initial gel diameter. In conclusion, these data show that inward eutrophic remodeling is a response to sustained contraction, which may involve collagen reorganization through β3-integrins. Copyright © 2004 S. Karger AG, Basel.