title: The effects of enalapril and losartan on mechanical ventilation-induced sympathoadrenal activation and oxidative stress in rats.
abstract: BACKGROUND
  Mechanical ventilation (MV) is a method of maintaining appropriate gas exchange in patients who are unable to sustain adequate alveolar ventilation. While lifesaving in the short-term, prolonged MV leads to altered cardiovascular responses and enhanced lung injury, but the exact mechanism is unknown. Therefore, we investigated the involvement of the sympathoadrenergic and renin-angiotensin system in MV-induced altered cardiovascular responses.
  
  
  METHODS
  Sprague-Dawley rats were divided into six groups: (1) spontaneous breathing (SB); (2) SB + enalapril (100 μg/kg intravenous infusion); (3) SB + losartan (100 μg/kg infusion); (4) 12 h of MV; (5) MV + enalapril; and (6) MV + losartan. After the animals were sacrificed, blood and tissue samples were collected. Tyrosine hydroxylase, dopamine beta hydroxylase, and neuropeptide Y were measured in adrenal medulla and hypothalamus, whereas AT1 was measured in lung tissues by Western blot. Norepinephrine enzyme-linked immunosorbent assay and total antioxidant capacity were assayed in plasma.
  
  
  RESULTS
  Our findings indicated that MV increases the sympathetic activation markers in adrenal medulla and hypothalamus. Moreover, oxidative stress was increased in lung and brain tissues. Treatment with enalapril or losartan reduced the lipid peroxidation in lung and brain tissues, while preserving the tissue glutathione content and plasma antioxidant capacity.
  
  
  CONCLUSIONS
  These data demonstrate that the inhibition of the renin-angiotensin system by enalapril or losartan may reduce the MV-induced increase in sympathetic activity markers and oxidative stress, and thus, may have a beneficial effect as adjuvant therapy.
authors.affiliation: Malcom Randall Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Gainesville, Florida; Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida; Department of Pharmacology, Marmara University School of Pharmacy, Istanbul, Turkey. Electronic address: haletoklu@yahoo.com.
authors.forename: Hale Zerrin
authors.initials: HZ
authors.lastname: Toklu
authors.affiliation: Department of Applied Physiology and Kinesiology, College of Health & Human Performance, University of Florida, Gainesville, Florida.
authors.forename: Oh-Sung
authors.initials: OS
authors.lastname: Kwon
authors.affiliation: Malcom Randall Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Gainesville, Florida; Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Sakarya
authors.affiliation: Department of Applied Physiology and Kinesiology, College of Health & Human Performance, University of Florida, Gainesville, Florida.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Powers
authors.affiliation: Malcom Randall Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Gainesville, Florida.
authors.forename: Katherine
authors.initials: K
authors.lastname: Llinas
authors.affiliation: Malcom Randall Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Gainesville, Florida; Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Kirichenko
authors.affiliation: Department of Applied Physiology and Kinesiology, College of Health & Human Performance, University of Florida, Gainesville, Florida.
authors.forename: Kurt J
authors.initials: KJ
authors.lastname: Sollanek
authors.affiliation: Department of Applied Physiology and Kinesiology, College of Health & Human Performance, University of Florida, Gainesville, Florida.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Wiggs
authors.affiliation: Department of Applied Physiology and Kinesiology, College of Health & Human Performance, University of Florida, Gainesville, Florida.
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Smuder
authors.affiliation: Department of Applied Physiology and Kinesiology, College of Health & Human Performance, University of Florida, Gainesville, Florida.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Talbert
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Scarpace
authors.affiliation: Malcom Randall Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Gainesville, Florida; Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida. Electronic address: ntumer@ufl.edu.
authors.forename: Nihal
authors.initials: N
authors.lastname: Tümer
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008171:Lung Diseases / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D013564:Sympathetic Nervous System / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D019808:Losartan
keywords: Angiotensin; Dopamine beta hydroxylase; Enalapril; Losartan; Mechanical ventilation; NPY; Noradrenergic; Norepinephrine; Sympathetic; Thyrosine hydroxylase