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This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/H2382    most recent 00132.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by de Frutos, S. Articles by González Bosc, L. Search for Related Content PubMed PubMed Citation Articles by de Frutos, S. Articles by González Bosc, L.

NFATc3 is required for intermittent hypoxia-induced hypertension

¹Vascular Physiology Group, Department of Cell Biology and Physiology, School of Medicine, and ²College of Pharmacy, University of New Mexico, Albuquerque, New Mexico

Submitted 7 February 2008 ; accepted in final form 19 March 2008

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% O₂-5% CO₂ 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 ( = 23.5 ± 6.1 mmHg), but not in KO mice ( = –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.

nuclear factor of activated T cells; hypercarbic; mouse; endothelin-1; sleep apnea