Integrins and Mechanosensitive Ion Channels in Reactive Dilation
Authors:
Joseph Chin, Douglas LandMentor:
Jeffrey Jasperse, Professor of Sports Medicine, Pepperdine UniversityWhen exercising, our arteries change diameter to supply contracting skeletal muscles with the oxygen and nutrients they need to perform under high activity conditions. The increase in blood flow to active muscle is primarily controlled by dilating feed arteries and arterioles. These arteries have been shown to respond to a period of reduced intraluminal pressure by dilating when pressure is returned to baseline levels. Previous work in our lab has shown that increasing the duration of pressure reduction amplifies the magnitude of reactive dilation. Previous experiments have shown that integrins also mediate at least part of the reactive dilation. We investigated how both endothelial and smooth muscle arterial integrins are involved in the mechanism of the reactive dilation. Rat soleus feed arteries were isolated and cannulated for in vitro videomicroscopic observation. Intraluminal pressure protocols were performed with decreases from a baseline of 115 cm of H2O to 14 cm of H2O for 30 sec, 1 min and 2 min periods followed by a return to baseline pressure. This was done in the presence of several blockers. 7 ml of air was passed through the arterial lumen for denudation which inhibited dilation to pressure reductions of 30 sec, (max: 29.8±10.8%, inhibited: 7.3±8.7%) 1 min, (max: 35.5 ±6.3%, inhibited: 20.4±10.9%). and 2 min. (max: 42.7±8.2%, inhibited: 21.0±11.7%) 0.5 mM F11 function blocking antibody (N=6) (β3 integrin subunit blocker) and 0.5 mM amiloride (N=9) (stretch activated channel blocker) failed to inhibit the reactive dilation. These data suggest that a large portion of the reactive dilation response is dependent upon the endothelium but that some other mechanism is also contributing to the reactive dilation response. These data also suggest that non-β3-integrin subunits are involved in this reaction but stretch activated channels are not involved.