Previously we found that high intraluminal pressure leads to production of reactive oxygen species (ROS) and also upregulates several components of the renin-angiotensin system in the wall of small arteries. We hypothesized that acute exposure of arterioles to high intraluminal pressure in vitro, via increasing ROS production, enhances the functional availability of type 1 angiontensin II (Ang II) receptors, resulting in sustained constrictions. In arterioles (~ 180 µm) isolated from rat skeletal muscle Ang II elicited dose-dependent constrictions, which decreased significantly by the second application (max.: from 59±4% to 26±5%, at 10^-8 M, p<0.05), in the presence of 80 mmHg of intraluminal pressure. In contrast, if the arterioles were exposed to high intraluminal pressure (160 mmHg, for 30 min) Ang II-induced constrictions remained substantial upon the second application (max.: 51±3% at 10^-8 M). In the presence Tiron and PEG-catalase, known to reduce the level of superoxide anion and hydrogen peroxide (H2O2), second applications of Ang II evoked similarly reduced constrictions, even after high pressure exposure (29±4% at 10^-8 M). Furthermore, when arterioles were exposed to H₂O₂ (for 30 min, 10^-7 M, at normal, 80 mmHg pressure), Ang II-induced constrictions remained substantial upon second applications (59±5% at 10^-8 M). These findings suggest that high pressure, likely via inducing H₂O₂ production increases the functional availability of AT1 receptors and thus enhances Ang II-induced arteriolar constrictions. We propose that in hypertension - regardless of etiology - high intraluminal pressure, via oxidative stress enhances the functional availability of AT1 receptors augmenting Ang II-induced constrictions.