Effect of Sodium Gradient on the Rate of Relaxation of Rat Mesenteric Small Arteries from Potassium Contractures

Abstract

We have measured the relaxation of rat mesenteric small arteries (internal diameter ca. 200 µm) from a potassium contracture under conditions where the transplasmalemmal sodium gradient was altered. Adjustment of the sodium gradient was made either by exposing vessels to ouabain (1 mM) for different periods to vary the intracellular sodium concentration (Na_i), or by varying the sodium concentrations of the relaxation solutions (Na_o). Under normal conditions (where we have previously shown Na_i is about 19 mM), vessels relaxed completely within 1 min in low sodium solutions (Na_o = 25 mM) using either sucrose, choline-Cl or MgCl₂ as substitutes. However, the relaxation (measured after 1 min) was reduced when sucrose substitution was used, and further experiments were made using this substitute. Here it was found that exposing vessels to ouabain, for example 90 min (thus increasing Nai to about 73 mM) and then performing the relaxation in a low sodium solution gave only about 50% relaxation after 1 min. Experiments with intermediate sodium concentrations in the relaxation medium showed that reduction to 100 mM had no significant effect on the relaxation, and that it was only below 50 mM that effects were most marked. The effects of altered sodium gradient were eliminated if the calcium concentration of the relaxation medium was zero. The results indicate that under normal physiological conditions, small changes in sodium gradient have little effect on calcium metabolism of rat mesenteric small arteries, but also that under extreme conditions net calcium extrusion does appear to be reduced by a reduced sodium gradient.

Regulation of cell calcium and contractility in mammalian arterial smooth muscle: the role of sodium‐calcium exchange.

“…Indeed, the data suggest that relatively small changes in A/iNa may alter the contractility of vascular smooth muscle by altering the sarcoplasmic reticulum stores of Ca2+, even though they do not affect tonic tension. The fact that similar effects are seen with low doses of ouabain in rat mesenteric small arteries (Aalkjaer & Mulvany, 1985) casts doubt on the view that 'small changes in sodium gradient have little effect on calcium metabolism of (these) arteries' (Petersen & Mulvany, 1984). The aforementioned tension measurements provide only indirect information about the influence of A#.Na on [Ca2+]i.…”

“…on arterial smooth muscle relaxation has been investigated in a few studies, (e.g. Bohr et al 1969;Petersen & Mulvany, 1984). The fact that relaxation from low-Na+ contractures was inhibited only when most of the external Na+ was removed has raised questions about the physiological significance of Na-Ca exchange in this tissue (e.g.…”

Vascular Na+/Ca2+exchanger: implications for the pathogenesis and therapy of salt-dependent hypertension

“…Recent topological analyses suggest that the NCX1 protein consists of nine transmembrane segments and a large central cytoplasmic loop, as illustrated in Fig. 1 (35, 38, (6,69,71). Nevertheless, some other reports suggest that Na ϩ /Ca 2ϩ exchange plays little role in cellular Ca 2ϩ homeostasis because of the relatively low activity of the vascular Na ϩ /Ca 2ϩ exchanger compared with other electrically excitable tissues (7,13,64).…”

Sodium–Calcium Exchanger in Pulmonary Artery Smooth Muscle Cells

“…[8][9][10][11][12][13] Similarly, pharmacological inhibition of NCX slows the relaxation of agonistevoked contraction and increases agonist-evoked contraction in systemic vascular muscle tissues. 8,9,[13][14][15][16][17][18][19][20][21][22] In addition, NCX may function in the reverse mode to cause or facilitate extracellular Ca 2+ influx in systemic vascular SMCs and to enhance agonist-induced contraction in systemic vascular tissues. [23][24][25][26][27] Consistent with the established importance of NCX1 in systemic vascular SMCs, a number of studies have shown that the hypertension is associated with changes in the activity of NCX in various types of arterial beds.…”

“…Inhibition of NCX by replacing extracellular Na + with Li + or using antisense oligonucleotides‐mediated gene knockdown significantly delays the removal of the elevated [Ca 2+ ] i following application of agonists and enhances agonist‐induced increases in [Ca 2+ ] i in systemic vascular SMCs 8–13 . Similarly, pharmacological inhibition of NCX slows the relaxation of agonist‐evoked contraction and increases agonist‐evoked contraction in systemic vascular muscle tissues 8,9,13–22 . In addition, NCX may function in the reverse mode to cause or facilitate extracellular Ca 2+ influx in systemic vascular SMCs and to enhance agonist‐induced contraction in systemic vascular tissues 23–27 .…”