Postnatal intermittent hypoxia and developmental programming of hypertension in spontaneously hypertensive Rats: The role of reactive oxygen species and L-Ca 2+ channels

Galia K. Soukhova-O'Hare, Roger V. Ortines, Yan Gu, Alexander D. Nozdrachev, Sumanth D. Prabhu, David Gozal

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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 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% O2 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 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.

Original languageEnglish
Pages (from-to)156-162
Number of pages7
JournalHypertension
Volume52
Issue number1
DOIs
StatePublished - Jul 1 2008

Keywords

  • Calcium channels
  • Hypertension
  • Intermittent hypoxia
  • Oxidative stress
  • Sleep apnea

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