Postnatal intermittent hypoxia and developmental programming of hypertension in spontaneously hypertensive rats: the role of reactive oxygen species and L-Ca2+ channels.

Academic Article

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(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.
  • Authors

    Published In

  • Hypertension  Journal
  • Keywords

  • Animals, Antioxidants, Blood Pressure, Body Weight, Calcium Channel Blockers, Calcium Channels, L-Type, Echocardiography, Heart Rate, Heart Ventricles, Hypertension, Hypoxia, Lipid Peroxides, Male, Metalloporphyrins, Nifedipine, Rats, Rats, Inbred SHR, Reactive Oxygen Species, Ventricular Remodeling
  • Digital Object Identifier (doi)

    Author List

  • Soukhova-O'Hare GK; Ortines RV; Gu Y; Nozdrachev AD; Prabhu SD; Gozal D
  • Start Page

  • 156
  • End Page

  • 162
  • Volume

  • 52
  • Issue

  • 1