Hypertension, Vol 22, 273-281, Copyright © 1993 by American Heart Association
JA Bevan
Our hypothesis is that flow-through hydraulic drag or shear stresses the
extracellular elements in the vascular wall. When the endothelium is
intact, this results in the release of endothelium-derived relaxing factor
and other substances, eg, prostanoids, from the endothelium. As in some
reports, after inhibition of nitric oxide synthase, flow effects are still
observed although diminished; the shear effect is extended mechanically to
the subendothelial tissues. Shear causes conformational changes in the
glycosaminoglycans by extending them from a randomly coiled aggregated
state to a more elongated condition along the line of flow. This elongation
and the consequent exposure of an increased number of cationic binding
sites on the glycosaminoglycans lead to changes in sodium binding. The
extent of the conformational change is influenced by the concentration of
calcium, an ion that not only competes with sodium at specific binding
sites but possibly cross- links the polysaccharide chains of the protein
saccharide complex. These complex interactions might account for the
cooperative, nonantagonistic interaction of sodium and calcium over the
physiological concentration range. Sodium binding is influenced by changes
in external sodium concentration, and this presumably accounts for the
sodium sensitivity of the flow response. Although glycosaminoglycans are
possibly the most studied in this regard, they are not the only candidates.
Other extracellular proteins, either in conjunction with glycosaminoglycans
or independently, might be involved. By mechanisms not yet identified,
these changes are signaled to the cell. We have proposed that in part, at
any rate, this may be related to the sodium concentration gradient.
ARTICLES
Flow regulation of vascular tone. Its sensitivity to changes in sodium and calcium
Department of Pharmacology, University of Vermont, College of Medicine, Burlington 05405-0068.
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