Abstract-Obstructive and central apneas during sleep are associated with chronic intermittent hypoxia (CIH) and increased cardiovascular morbidity. Spontaneously hypertensive rats exposed to CIH during postnatal days 4 to 30 develop exaggerated hypertension as adults. We hypothesized that reactive oxygen species and altered L-Ca 2ϩ channel activity may underlie the postnatal programming of exaggerated blood pressure and cardiac remodeling. Newborn male spontaneously hypertensive rats were exposed to CIH (10% and 21% O 2 alternating every 90 seconds, 12 h/d, for postnatal days 4 to 30) or normoxia (room air). In each condition, spontaneously hypertensive rats received daily (SC) 1 of 3 treatments: L-calcium channel blocker nifedipine (5 mg/kg), superoxide dismutase mimetic MnTMPyP pentachloride (10 mg/kg), or vehicle (polyethylene glycol). Blood pressure was evaluated monthly for 6 months after birth, and echocardiographic assessments were conducted at 6 months of age. CIH vehicle-treated rats presented higher systolic blood pressure (187Ϯ5 mm Hg) as compared with normoxic vehicle treated controls (163Ϯ2 mm Hg; PϽ0.001). Postnatal CIH elicited marked increases in left ventricular wall thickness in a pattern of concentric hypertrophy with augmented systolic contractility. The treatment with nifedipine in the CIH group attenuated blood pressure (159Ϯ2 mm Hg; PϽ0.001) and normalized left ventricular wall thickness and systolic function, whereas the treatment with SOD mimetic decreased blood pressure (165Ϯ2 mm Hg; PϽ0.001) and reduced left ventricular wall thickness without changes in the systolic function. We conclude that Ca 2ϩ and reactive oxygen species-mediated signaling during intermittent hypoxia are critical mechanisms underlying postnatal programming of an increased severity of hypertension and hypertrophic cardiac remodeling in a genetically susceptible rodent model. Key Words: intermittent hypoxia Ⅲ calcium channels Ⅲ oxidative stress Ⅲ sleep apnea Ⅲ hypertension I ntermittent hypoxia (IH) during sleep is one of the characteristics of sleep apnea that is associated with substantial cardiovascular (CV) morbidity, such as hypertension and heart failure. Sleep-disordered breathing with apneic episodes and intermittent hypoxemia are frequently encountered in young children 1 ; however, the potential consequences of postnatal IH on adult CV dysfunction are not clear. There is accumulating evidence that IH is associated with an increased oxidative stress [2][3][4][5][6] and that redox signaling during this condition has been extensively implicated in CV pathophysiology, including some forms of hypertension and cardiac function. 2,7-9 Perinatal L-arginine and antioxidant supplements were shown to reduce blood pressure (BP) in adult spontaneously hypertensive rats (SHRs), suggesting a critical role of oxidative status during perinatal development in programming BP later in life. 10 In previous work from our laboratory, we demonstrated that SHRs exposed for the first 30 days of postnatal life to a chronic intermitt...