What is the clinical evidence from this study?

Study design: Other. Intervention: Steady laminar shear stress vs. Oscillatory shear stress. Primary outcome: Na-K-Cl cotransporter activity and protein expression.

January 1, 2001

Flow-induced expression of endothelial Na-K-Cl cotransport: dependence on K+ and Cl− channels

Key Result

Steady shear stress increased BAEC Na-K-Cl cotransporter protein levels 2- to 4-fold and activity 1.5- to 1.8-fold compared to oscillatory flow, an effect abolished by K+ and Cl- channel blockers.

Structured PICO

Does steady shear stress modulate the expression and activity of the Na-K-Cl cotransporter in bovine aortic endothelial cells?

Population

Confluent bovine aortic endothelial cell (BAEC) monolayers

Intervention

Steady shear stress (19 dyn/cm²) or purely oscillatory shear stress (0 +/- 19 dyn/cm²) for 6-48 h, with or without flow-sensitive K(+) and Cl(-) channel pharmacological blockers

Comparator

Oscillatory flow or absence of pharmacological blockers

Outcome

Na-K-Cl cotransporter activity and protein expressionsurrogate

Steady shear stress increases Na-K-Cl cotransporter expression and activity in endothelial cells through mechanisms dependent on flow-activated K(+) and Cl(-) channels.

Abstract

Steady laminar shear stress has been shown previously to markedly increase Na-K-Cl cotransporter mRNA and protein in human umbilical vein endothelial cells and also to rapidly increase endothelial K(+) and Cl(-) channel conductances. The present study was done to evaluate the effects of shear stress on Na-K-Cl cotransporter activity and protein expression in bovine aortic endothelial cells (BAEC) and to determine whether changes in cotransporter expression may be dependent on early changes in K(+) and Cl(-) channel conductances. Confluent BAEC monolayers were exposed in a parallel-plate flow chamber to either steady shear stress (19 dyn/cm(2)) or purely oscillatory shear stress (0 +/- 19 dyn/cm(2)) for 6-48 h. After shearing, BAEC monolayers were assessed for Na-K-Cl cotransporter activity or were subjected to Western blot analysis of cotransporter protein. Steady shear stress led to a 2- to 4-fold increase in BAEC cotransporter protein levels and a 1.5- to 1.8-fold increase in cotransporter activity, increases that were sustained over the longest time periods studied. Oscillatory flow, in contrast, had no effect on cotransporter protein levels. In the presence of flow-sensitive K(+) and Cl(-) channel pharmacological blockers, the steady shear stress-induced increase in cotransporter protein was virtually abolished. These results suggest that shear stress modulates the expression of the BAEC Na-K-Cl cotransporter by mechanisms that are dependent on flow-activated ion channels.

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