Shear Stress Attenuates Inward Remodeling in Cultured Mouse Thoracodorsal Arteries in an eNOS-Dependent, but Not
Robin C Looft-Wilson1,2,3,4, Janelle E Billig5, William C Sessa6,7,8
1Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA, rlooft@wm.edu.
Background:
Arteries chronically constricted in culture remodel to smaller diameters. Conversely, elevated luminal shear stress (SS) promotes outward remodeling of arteries in vivo and prevents inward remodeling in culture in a nitric oxide synthase (NOS)-dependent manner.
Objectives:
To determine whether SS-induced prevention of inward remodeling in cultured arteries is specifically eNOS-dependent and requires dilation, and whether SS alters the expression of eNOS and other genes potentially involved in remodeling.
Methods:
Female mouse thoracodorsal arteries were cannulated, pressurized to 80 mm Hg, and cultured for 2 days with low SS (<7 dyn/cm2), high SS (≥15 dyn/cm2), high SS + L-NAME (NOS inhibitor, 10-4 M), or high SS in arteries from eNOS-/- mice. In separate arteries cultured 1 day with low or high SS, eNOS and connexin (Cx) 37, Cx40, and Cx43 mRNA were assessed with real-time PCR.
Results:
High SS caused little change in passive diameters after culture (-4.7 ± 2.0%), which was less than low SS (-18.9 ± 1.4%; p < 0.0001), high SS eNOS-/- (-18.0 ± 1.5; p < 0.001), or high SS + L-NAME (-12.0 ± 0.6%; nonsignificant) despite similar constriction during culture. Cx37 mRNA expression was increased (p < 0.05) with high SS, but other gene levels were not different.
Conclusions:
eNOS is involved in SS-induced prevention of inward remodeling in cultured small arteries. This effect does not require NO-mediated dilation. SS increased Cx37.
