Recent studies from our laboratory demonstrated the importance of mechanosensitive Epithelial Na⁺ Channel (ENaC) proteins in pressure-induced constriction in renal and cerebral arteries. ENaC proteins are closely related to Acid Sensing Ion Channel 2 (ASIC2), a protein known to be required for normal mechanotransduction in certain sensory neurons. However, the role of ASIC2 protein in pressure-induced constriction has never been addressed. The goal of the current study was to investigate the role of ASIC2 proteins in pressure-induced, or myogenic, constriction in the mouse middle cerebral arteries (MCA) from ASIC2 wildtype (+/+), heterozygous (+/-) and null (-/-) mice. Constrictor responses to KCl (20 - 80 mM) and phenylephrine (10-7 - 10-4 M) were not different among groups. However, vasoconstrictor responses to increases in intraluminal pressure (15 - 90 mm Hg) were impaired in MCAs from ASIC2 -/- and +/- mice. At 60 and 90 mm Hg, MCAs from ASIC2 +/+ mice generated 13.7 ± 2.1 and 15.8 ± 2.0 % tone, ASIC2 -/- mice generated 7.4 ± 2.8 and 12.5 ± 2.4 % tone, respectively. Surprisingly, MCAs from ASIC2 +/- mice generated 1.2 ± 2.2 and 3.9 ± 1.8% tone at 60 and 90 mm Hg. The reason underlying the total loss of myogenic tone in the ASIC2 +/- is not clear, although the loss of mechanosensitive ENaC and ENaC proteins may be a contributing factor. These results demonstrate that normal ASIC2 expression is required for normal pressure-induced constriction in the MCA. Furthermore, ASIC2 may be involved in establishing the basal level of myogenic tone.