on May 12, 2005
Published online before print May 12, 2005, doi: 10.1161/01.ATV.0000170136.71970.5f
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Submitted on November 25, 2004
Accepted on May 2, 2005
PECAM-1 Mediates NO-Dependent Dilation of Arterioles to High Temporal Gradients of Shear Stress
Zsolt Bagi ;
From the Department of Physiology (Z.B., G.K., A.K.), New York Medical College, Valhalla, NY; the La Jolla Bioengineering Institute (J.A.F., J.-C.Y., C.R.W.), La Jolla, Calif; and the Department of Pathophysiology (Z.B.), Semmelweis University, Budapest Hungary.
* To whom correspondence should be addressed. E-mail: koller{at}nymc.edu.
Objective--In response to changes in wall shear stress (WSS) the vascular endothelium releases several factors, among others nitric oxide. On the basis of studies of endothelial cells in culture, suggesting that platelet endothelial cell adhesion molecule-1 (PECAM-1) is specifically involved in sensing and coupling high temporal gradients of fluid shear stress with activation of eNOS, we hypothesized that dilations of isolated skeletal muscle arterioles from wild-type (WT) and PECAM-1 knockout mice (PECAM-KO) will be reduced to rapid increases in WSS elicited by increases in perfusate flow.
Methods and Results--Small and large step increases in flow resulted in substantial dilations in arterioles of WT mice (45±4%), but they were markedly reduced in arterioles of PECAM-KO mice (22±5%). The initial slope of dilations, when WSS increased rapidly, was greater in vessels of WT than those of PECAM-KO mice (slopes: 0.378 and 0.094, respectively), whereas the second phase of dilations, when flow/shear stress was steady, was similar in the two groups (slopes: 0.085 and 0.094, respectively). Inhibition of eNOS significantly reduced the initial phase of dilations in arterioles from WT, but not from those of PECAM-KO mice. The calcium ionophore A23187 elicited similar NO-mediated dilation in both WT and PECAM-KO mice.
Conclusions--In isolated arterioles of PECAM-KO mice activation of eNOS and consequent dilation by agonists is maintained, but the dilation to high temporal gradients of wall shear stress elicited by increases in perfusate flow is reduced. Thus, we propose that PECAM-1 plays an important role in the ability of the endothelium to sense and couple high temporal gradients of wall shear stress to NO-mediated arteriolar dilation during changes in blood flow in vivo.
Key words: PECAM-1 • arteriole • endothelium • flow-induced dilation • nitric oxide
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