Four Weeks of Repetitive Acute Hypoxic Preconditioning Did Not Alleviate Allergen-Induced Airway Dysfunction in Rats
Authors List
Ruolin Song1; Oleg Broytman1; Nicole Liang1; Jonathan Setzke1; Christopher Setzke1; Gabriela Wojdyla1; David F. Pegelow2; Fauzia Osman, MPH1; Ronald L. Sorkness1,3; Jyoti J. Watters4; Mihaela Teodorescu1,5
1Department of Medicine and 2Department of Pediatrics, School of Medicine and Public Health, 3School of Pharmacy and 4Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin—Madison, Wisconsin, USA; 5William S. Middleton Memorial VA Medical Center, Madison, Wisconsin, USA.
Rationale
Clinical case series suggest beneficial effects of low-dose intermittent hypoxia in asthma. We tested cardiopulmonary effects of repetitive acute hypoxic preconditioning (RAHP) during allergic inflammation.
Methods
Brown Norway rats were exposed to 4-week RAHP or normoxia (SHAM), concurrent with weekly house dust mites (HDM) or saline (SAL) challenges. We assessed methacholine responses and lung HIF-1α expression at endpoint, and weekly blood pressure (BP).
Results
RAHP relative to SHAM: 1) in HDM-challenged rats, showed no protection against HDM-induced airway dysfunction, seemed to elicit hypertensive side-effects (week 4 mean BP average difference = 10.51 mmHg, p = 0.09), and did not impact HIF-1α expression; 2) in SALchallenged rats, attenuated airway response to methacholine and BP (week 4 mean BP average difference = -8.72 mmHg, p = 0.04), and amplified HIF-1α expression (p = 0.0086).
Conclusions
Four weeks of RAHP did not mitigate the allergen-induced lower airway dysfunction and detrimentally affected BP. However, it elicited beneficial cardiopulmonary responses in SAL-challenged rats, concurrent with increased HIF-1α expression.
Funding: This work was supported by the Department of Medicine, University of Wisconsin School of Medicine and Population Health, Madison, Wisconsin and by the Merit Review Award # 1I01BX002880-01A2 (to MT) from the United States Department of Veterans Affairs, Biomedical Laboratory Research and Development Service, with additional resources and use of facilities at the William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin. The content of this abstract is solely the responsibility of the authors and does not represent the views of the Department of Veterans Affairs or the United States Government.
Ruolin Song1; Oleg Broytman1; Nicole Liang1; Jonathan Setzke1; Christopher Setzke1; Gabriela Wojdyla1; David F. Pegelow2; Fauzia Osman, MPH1; Ronald L. Sorkness1,3; Jyoti J. Watters4; Mihaela Teodorescu1,5
1Department of Medicine and 2Department of Pediatrics, School of Medicine and Public Health, 3School of Pharmacy and 4Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin—Madison, Wisconsin, USA; 5William S. Middleton Memorial VA Medical Center, Madison, Wisconsin, USA.
Rationale
Clinical case series suggest beneficial effects of low-dose intermittent hypoxia in asthma. We tested cardiopulmonary effects of repetitive acute hypoxic preconditioning (RAHP) during allergic inflammation.
Methods
Brown Norway rats were exposed to 4-week RAHP or normoxia (SHAM), concurrent with weekly house dust mites (HDM) or saline (SAL) challenges. We assessed methacholine responses and lung HIF-1α expression at endpoint, and weekly blood pressure (BP).
Results
RAHP relative to SHAM: 1) in HDM-challenged rats, showed no protection against HDM-induced airway dysfunction, seemed to elicit hypertensive side-effects (week 4 mean BP average difference = 10.51 mmHg, p = 0.09), and did not impact HIF-1α expression; 2) in SALchallenged rats, attenuated airway response to methacholine and BP (week 4 mean BP average difference = -8.72 mmHg, p = 0.04), and amplified HIF-1α expression (p = 0.0086).
Conclusions
Four weeks of RAHP did not mitigate the allergen-induced lower airway dysfunction and detrimentally affected BP. However, it elicited beneficial cardiopulmonary responses in SAL-challenged rats, concurrent with increased HIF-1α expression.
Funding: This work was supported by the Department of Medicine, University of Wisconsin School of Medicine and Population Health, Madison, Wisconsin and by the Merit Review Award # 1I01BX002880-01A2 (to MT) from the United States Department of Veterans Affairs, Biomedical Laboratory Research and Development Service, with additional resources and use of facilities at the William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin. The content of this abstract is solely the responsibility of the authors and does not represent the views of the Department of Veterans Affairs or the United States Government.
