| First Author | de Frutos S | Year | 2008 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 294 |
| Issue | 5 | Pages | H2382-90 |
| PubMed ID | 18359899 | Mgi Jnum | J:136058 |
| Mgi Id | MGI:3795039 | Doi | 10.1152/ajpheart.00132.2008 |
| Citation | de Frutos S, et al. (2008) NFATc3 is required for intermittent hypoxia-induced hypertension. Am J Physiol Heart Circ Physiol 294(5):H2382-90 |
| abstractText | Sleep apnea, defined as intermittent respiratory arrest during sleep, is associated with increased incidence of hypertension and peripheral vascular disease. Exposure of rodents to brief periods of intermittent hypercarbia/hypoxia (H-IH) during sleep mimics the cyclical hypoxia-normoxia of sleep apnea. Endothelin-1, an upstream activator of nuclear factor of activated T cells (NFAT), is increased during H-IH. 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(2)-5% CO(2) for 7 h/day) induces systemic hypertension in mice [mean arterial pressure (MAP) = 97 +/- 2 vs. 124 +/- 2 mmHg, P < 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 (Delta = 23.5 +/- 6.1 mmHg), but not in KO mice (Delta = -3.9 +/- 5.7). These results indicate that H-IH-induced increases in MAP require NFATc3 and that NFATc3 may contribute to the vascular changes associated with H-IH-induced hypertension. |
