Postnatal Intermittent Hypoxia and Developmental Programming of Hypertension in Spontaneously Hypertensive Rats The Role of Reactive Oxygen Species and L-Ca(2+) Channels

作者：Soukhova O'Hare Galia K; Ortines Roger V; Gu Yan; Nozdrachev Alexander D; Prabhu Sumanth D; Gozal David^*

来源：Hypertension, 2008, 52(1): 156-162.

DOI：10.1161/HYPERTENSIONAHA.108.110296

• intermittent hypoxia
• calcium channels
• oxidative stress
• sleep apnea
• hypertension

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(2+) 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 (187 +/- 5 mm Hg) as compared with normoxic vehicle treated controls (163 +/- 2 mm Hg; P < 0.001). 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 (159 +/- 2 mm Hg; P < 0.001) and normalized left ventricular wall thickness and systolic function, whereas the treatment with SOD mimetic decreased blood pressure (165 +/- 2 mm Hg; P < 0.001) and reduced left ventricular wall thickness without changes in the systolic function. We conclude that Ca(2+) 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. (Hypertension. 2008;52:156-162.)

• 出版日期2008-7