Flow regulation of vascular tone. Its sensitivity to changes in sodium and calcium.

Abstract

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.

Effect of a High Salt Diet on Microvascular Antioxidant Enzymes

“…The mechanism that underlies the apparent salt-dependent decrease in microvascular Cu/Zn SOD activity is unclear. In HS rats, plasma sodium levels are not elevated for more than 2–3 days [50, 51], but a resulting sodium accumulation in vessel walls may lead to a more sustained change in the endothelial microenvironment [52]. Since most vascular wall sodium is extracellular and bound to membrane-associated glycosaminoglycans [53], increased sodium binding could influence endothelial cell function by altering the charge distribution or some other property of endothelial glycocalyx [52].…”

“…In HS rats, plasma sodium levels are not elevated for more than 2–3 days [50, 51], but a resulting sodium accumulation in vessel walls may lead to a more sustained change in the endothelial microenvironment [52]. Since most vascular wall sodium is extracellular and bound to membrane-associated glycosaminoglycans [53], increased sodium binding could influence endothelial cell function by altering the charge distribution or some other property of endothelial glycocalyx [52]. Although speculative, such changes could directly influence Cu/Zn SOD activity, since the Cu/Zn SOD that is thought to be most important for regulating NO bioavailability in the vasculature is an extracellular glycoprotein that mainly exists bound to the endothelial cell glycocalyx [54].…”

High Sodium Intake Decreases Pressure-Induced (Myogenic) Tone and Flow-Induced Dilation in Resistance Arteries From Hypertensive Rats

“…10 -13 Previous studies have shown a specific sensitivity of flow-induced dilation and myogenic tone to small changes in extracellular sodium concentration. 1,14 We hypothesized that flow-induced dilation and myogenic tone might be selectively influenced by high salt intake. We used mesenteric resistance arteries from spontaneously hypertensive rats (SHR) submitted to high dietary salt intake.…”

Reactivity of the isolated perfused rat tail vascular bed

“…Flow has been described as a stimulus for the endothelial cells to liberate vasodilator substances (9-11). On the other hand, the increase in pressure stretches the endothelial layer, inducing the release of endotheliumderived contraction factor (EDCF) (9,10,12). In our protocol, the increase in pressure may release endothelial EDCF that acts synergistically with PE by potentiating the pressure increment produced by flow.…”