title: Influence of intermittent hypoxia on myocardial and hepatic P-glycoprotein expression in a rodent model.
abstract: OBJECTIVE
  Patients with obstructive sleep apnea who receive drug therapy for cardiovascular disease may experience resistant hypertension, arrhythmias, or more severe heart failure, and many of the drugs used to treat these conditions are substrates for P-glycoprotein (P-gp) transporters. Therefore, we sought to determine if intermittent hypoxia, which mimics obstructive sleep apnea, would upregulate myocardial and hepatic P-gp expression and Abcb1a and Abcb1b messenger RNA (mRNA) expression (genes that encode for P-gp) in an animal model.
  
  
  METHODS
  Prospective, randomized, blinded, parallel-design animal study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Thirty adult, male Sprague-Dawley rats.
  
  
  METHODS
  Rats were assigned to either 2 weeks of intermittent hypoxia exposure similar to sleep apnea (12 rats) or no hypoxia exposure (controls, 18 rats).
  
  
  RESULTS
  After intermittent hypoxia or normoxia exposure, the rats were anesthetized. Heart and liver were harvested, and small samples were taken from the left ventricle (heart) and the liver for analysis. Expression of P-gp was measured by Western blotting, whereas Abcb1a and Abcb1b mRNA expression was assessed by real-time polymerase chain reaction. Band density of myocardial (but not hepatic) P-gp expression (standardized by beta-actin) was significantly higher in hypoxic rats than in control rats (p=0.03). Quantitative polymerase chain reaction revealed that myocardial and hepatic Abcb1a and myocardial Abcb1b mRNA expression were significantly increased in hypoxic rats compared with controls (p<0.05).
  
  
  CONCLUSIONS
  Myocardial P-gp expression and myocardial and hepatic Abcb1a mRNA expression were significantly increased after 2 weeks of intermittent hypoxia. Hypoxia-induced increases in P-gp expression may partially explain drug-resistant cardiovascular disease in patients with obstructive sleep apnea.
authors.affiliation: Schools of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705, USA. jmdopp@pharmacy.wisc.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Dopp
authors.forename: John J
authors.initials: JJ
authors.lastname: Moran
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Abel
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Wiegert
authors.forename: John B
authors.initials: JB
authors.lastname: Cowgill
authors.forename: E Burt
authors.initials: EB
authors.lastname: Olson
authors.forename: J Jason
authors.initials: JJ
authors.lastname: Sims