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(Circulation Research. 1996;78:945-946.)
© 1996 American Heart Association, Inc.

Articles

NO Flow Helps Clear Murky Waters?

Peter F. Davies

From the Department of Pathology, University of Chicago School of Medicine, Chicago, Ill.

Correspondence to Dr Peter Davies, Department of Pathology, University of Chicago School of Medicine, 5841 S Maryland Ave, Chicago, IL 60637.

Key Words: Editorials • nitric oxide • calcium • shear stress • tyrosine kinase • endothelium

	Introduction

 
The relationships between blood flow and arterial tone have fascinated physiologists for decades. Increased and decreased flows result in vessel relaxation and contraction, respectively. Consequently, when pharmacological or neurochemical events constrict an artery, the increased flow and shear stress stimulate a compensatory vasorelaxation to restore the vessel tone, returning the average shear stress to near its previous level. The endothelium is now recognized as the principal vascular signal transducer that responds to changes of flow,¹ including the release of nitric oxide (NO). Endothelium-derived NO then acts on smooth muscle guanylate cyclase to relax the vessel. There is much evidence to suggest that shear stress is the principal stimulus for activation of endothelial NO synthase (eNOS), the enzyme responsible for converting arginine to citrulline and NO. However, the mechanisms that lead from hemodynamic forces at the endothelial luminal surface to the activation of eNOS remain murky. Although sustained increases in flow stimulate eNOS gene expression, these transcriptional mechanisms are likely to be downstream from the rapid (and reversible) signaling required for minute-to-minute adjustments of arterial diameter. Efforts have therefore been concentrated on second messenger pathways studied principally in cultured cells. In this issue of Circulation Research, Ayajiki et al² (in Rudi Busse's group at Frankfurt, Germany) report investigations of flow-induced NO release in arterial tissues. They confirm earlier signaling mechanisms elucidated in vitro while raising a number of questions pertinent to real tissues.

In cultured cells, NO production in response to shear stress is biphasic.³ The initial peak of NO . . . [Full Text of this Article]