Acute mechanoadaptation of vascular smooth muscle cells in response to continuous arteriolar vasoconstriction: implications for functional remodeling.

Abstract

Arterioles exposed to norepinephrine (NE) for 4 h exhibit incomplete relaxation on removal of the agonist. We hypothesized that this is due to a mechanoadaptation process associated with active repositioning of vascular smooth muscle cells (VSMCs) within the vascular wall. Isolated arterioles were exposed to NE (10(-5.5) M) for either 5 min (n = 7) or 4 h (n = 13). During the 5-min exposure, vessel diameter was reduced to 61 +/- 2.6%, and cells shortened to 76.3 +/- 3.8% of control. After NE removal, vessel diameter and cell length returned to control values, which indicated that during acute vasoconstriction cells shorten and relengthen in a reversible fashion. In contrast, when NE exposure lasted 4 h, vessels did not return to control diameter, but VSMCs returned to control length after NE removal. During the 4-h constriction, 56% of the VSMCs began returning to control length, and the overlap between VSMCs increased, which indicated that cellular repositioning had occurred in the presence of the maintained constriction. Thus, in response to prolonged constriction, VSMCs undergo a mechanoadaptation process involving "length autoregulation" that would be energetically favorable for maintenance of a reduced diameter and may provide a mechanism for the development of eutrophic remodeling of the vascular wall.