We have investigated effects of altered extracellular sodium, intracellular sodium concentration, and membrane potential on the contractile responses of rat isolated mesenteric small arteries (internal diameter ca. 200 microns), when mounted as ring preparations on an isometric myograph. To avoid possible neural effects, all vessels were denervated in vitro using 6-hydroxydopamine. In unstimulated vessels, exposure to low-Na+ solutions (25 mM sodium, sucrose, or choline-substituted) did not cause any response nor did exposure to ouabain (1 mM) for 1 hour [when intracellular sodium concentration increased to 64 mmol/(liter-cell)]. However, a response was obtained if ouabain-exposed vessels were subjected to low-sodium solutions (ca. 15% of maximal response). The magnitude of the response was dependent on the ratio of intracellular to extracellular sodium and was not inhibitable by the calcium blockers, felodipine (1 nM) or D600 (10 microM). This response could therefore be explained in terms of Na-Ca exchange mechanism. The responses of activated vessels to ouabain and to low-sodium solutions were also investigated. The responses of vessels to submaximal doses of noradrenaline or potassium were potentiated acutely by ouabain (by 10-30% of the maximal response), even if the extracellular sodium was reduced to 25 mM. In all cases, the potentiation by ouabain was accompanied by a depolarization (3-12 mV). However, only in the case of noradrenaline-activated vessels with normal extracellular sodium was the potentiation accompanied by an increase in intracellular sodium [by ca. 7 mmol/(liter-cell)]. Moreover, the latter response was inhibited by felodipine and D600. The results suggest that Na-Ca exchange mechanisms may be present in these vessels but that they only play a role under extreme conditions; under normal conditions the effect of ouabain on activated vessels seems to be primarily due to its depolarizing effect, and not to its effect on intracellular sodium.