We have reported that eucapnic intermittent hypoxia (E-IH) causes systemic hypertension, elevates plasma endothelin 1 (ET-1) levels, augments vascular reactivity to ET-1 and that a non-specific ET-1 receptor antagonist acutely lowers blood pressure in E-IH-exposed rats. However, the effect of chronic ET-1 receptor inhibition has not been evaluated and the ET receptor subtype mediating the vascular effects has not been established. We hypothesized that E-IH causes systemic hypertension through increased ET-1 activation of vascular ET_A receptors. We found that mean arterial pressure (MAP) increased after 14 days of 7 hrs/day E-IH exposure (109 ± 2 to 137 ± 4 mmHg, p<0.005), but did not change in Sham exposed rats. The ET_A receptor antagonist BQ-123 (10 to 1000 nmol/kg, i.v.) acutely decreased MAP dose-dependently in conscious E-IH but not Sham rats and continuous infusion of BQ-123 (100 nmol/kg./day s.c. for 14 days) prevented E-IH induced increases in MAP. ET-1-induced constriction was augmented in small mesenteric arteries from rats exposed 14 days to E-IH compared to those from Sham rats. Constriction was blocked by ET_AR antagonist BQ-123 (10 µM) but not by ET_BR antagonist BQ-788 (100 µM). ETA receptor mRNA content was greater in renal medulla and coronary arteries from E-IH rats. ETB receptor mRNA was not different in any tissues examined while ET-1 mRNA was increased in the heart and in the renal medulla. Thus augmented ET-1-dependent vasoconstriction via vascular ET_AR appears to elevate blood pressure in E-IH-exposed rats.