The wall stiffness of arteries and arterioles adapts to the long-term demands imposed by local intravascular pressure. We investigated whether substances capable of inducing acute and long-term effects on arterial wall stiffness are released locally into the bloodstream in response to an acute marked increase in local intravascular pressure in the blood vessels of the human arm. Experiments were performed on ten subjects positioned in a pressure chamber with one arm extended through a hole in the chamber door and kept at normal atmospheric pressure. Intravascular pressure was increased in the arm, by a stepwise increase in chamber pressure up to +150 mmHg. Diameter and flow were measured in the brachial artery by Doppler ultrasonography. Blood samples were drawn simultaneously from both arms before, during, immediately after and 2 h after the release of the chamber pressure. Plasma levels of endothelin-1 (ET-1), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2) and angiotensin II (Ang-II) were measured. Elevation of chamber pressure by 150 mmHg increased local arterial distending pressure to about 220–260 mmHg, resulting in an increase in brachial artery diameter of 9% and flow of 246%. The pressure stimulus increased the plasma levels of ET-1 and Ang-II, but not of VEGF-A or FGF-2 in the test arm. The local release of the vasoconstrictors ET-1 and Ang-II in response to markedly increased distending pressure may reflect one mechanism behind adaptation to acute and long-term changes in intravascular pressure.