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Therefore, we hypothesized that NFATc3 is activated by H-IH and is required for H-IH-induced hypertension. Consistent with this hypothesis, we found that H-IH (20 brief exposures per hour to 5% O<jats:sub>2<\/jats:sub>-5% CO<jats:sub>2<\/jats:sub>for 7 h\/day) induces systemic hypertension in mice [mean arterial pressure (MAP) = 97 \u00b1 2 vs. 124 \u00b1 2 mmHg, P &lt; 0.05, n = 5] and increases NFATc3 transcriptional activity in aorta and mesenteric arteries. Cyclosporin A, an NFAT inhibitor, and genetic ablation of NFATc3 [NFATc3 knockout (KO)] prevented NFAT activation. More importantly, H-IH-induced hypertension was attenuated in cyclosporin A-treated mice and prevented in NFATc3 KO mice. MAP was significantly elevated in wild-type mice (\u0394 = 23.5 \u00b1 6.1 mmHg), but not in KO mice (\u0394 = \u22123.9 \u00b1 5.7). 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