High-salt diet is often associated with increases in arterial pressure, and a role for endothelin (ET)-1 in salt-sensitive hypertension has been suggested; however, the vascular mechanisms involved are unclear. We investigated whether ET increases the sensitivity of the mechanisms of vascular contraction to changes in dietary salt intake. Active stress and ⁴⁵ Ca ²⁺ influx were measured in endothelium-denuded aortic strips of male Sprague-Dawley rats not treated or chronically infused intravenously with ET (5 pmol/kg per minute) and fed either normal-sodium diet (NS, 1%) or high-sodium diet (HS, 8%) for 9 days. Phenylephrine (Phe) caused increases in active stress that were similar in NS and HS, but were greater in NS/ET (maximum, 10.5±0.7) than in NS (maximum, 7.4±0.9) rats, and further enhanced in HS/ET (maximum, 14.4±1.1) compared with HS rats (maximum, 8.0±0.8×10 ⁴ N/m ² ). Phe was more potent in causing contraction in NS/ET than in NS rats and in HS/ET than in HS rats. In Ca ²⁺ -free (2 mmol/L EGTA) Krebs, stimulation of intracellular Ca ²⁺ release by Phe (10 ⁻⁵ mol/L) or caffeine (25 mmol/L) caused a transient contraction that was not significantly different in all groups of rats. In contrast, membrane depolarization by high-KCl solution, which stimulates Ca ²⁺ entry from the extracellular space, caused greater contraction in ET-infused rats, particularly those on HS diet. Phe (10 ⁻⁵ mol/L) caused an increase in ⁴⁵ Ca ²⁺ influx that was greater in NS/ET (27.9±1.7) than in NS (20.1±1.8) rats and further enhanced in HS/ET (35.2±1.8) compared with HS rats (21.8±1.9 μmol/kg/min). The Phe-induced ⁴⁵ Ca ²⁺ influx-stress relation was not different between NS and HS rats, but was enhanced in ET-infused rats particularly those on HS. The enhancement of the ⁴⁵ Ca ²⁺ influx–active stress relation in ET-infused rats was not observed in vascular strips treated with the protein kinase C inhibitor GF109203X or calphostin C (10 ⁻⁶ mol/L). Thus, low-dose infusion of ET, particularly during HS, is associated with increased vascular reactivity that involves Ca ²⁺ entry from the extracellular space, but not Ca ²⁺ release from the intracellular stores. The ET-induced enhancement of the Ca ²⁺ influx-stress relation particularly during HS suggests activation of other mechanisms in addition to Ca ²⁺ entry, possibly involving protein kinase C. The results suggest that ET increases the sensitivity of the mechanisms of vascular smooth muscle contraction to high dietary salt intake and may, in part, explain the possible role of ET in salt-sensitive hypertension.