title: Sildenafil reduces signs of oxidative stress in pulmonary arterial hypertension: Evaluation by fatty acid composition, level of hydroxynonenal and heart rate variability.
abstract: Pulmonary arterial hypertension (PAH) is a rare multifactorial disease with an unfavorable prognosis. Sildenafil therapy can improve functional capacity and pulmonary hemodynamics in PAH patients. Nowadays, it is increasingly recognized that the effects of sildenafil are pleiotropic and may also involve changes of the pro-/antioxidant balance, lipid peroxidation and autonomic control. In present study we aimed to assess the effects of sildenafil on the fatty acids (FAs) status, level of hydroxynonenal (HNE) and heart rate variability (HRV) in PAH patients. Patients with PAH were characterized by an increase in HNE and changes in the FAs composition with elevation of linoleic, oleic, docosahexanoic acids in phospholipids as well as reduced HRV with sympathetic predominance. Sildenafil therapy improved exercise capacity and pulmonary hemodynamics and reduced NT-proBNP level in PAH. Antioxidant and anti-inflammatory effects of sildenafil were noted from the significant lowering of HNE level and reduction of the phopholipid derived oleic, linoleic, docosahexanoic, docosapentanoic FAs. That was also associated with some improvement of HRV on account of the activation of the neurohumoral regulatory component. Incomplete recovery of the functional metabolic disorders in PAH patients may be assumed from the persistent increase in free FAs, reduced HRV with the sympathetic predominance in the spectral structure after treatment comparing to control group. The possibilities to improve PAH treatment efficacy through mild stimulation of free radical reactions and formation of hormetic reaction in the context of improved NO signaling are discussed.
authors.affiliation: Department of Propedeutics of Internal Medicine #2, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine. Electronic address: khrystyna_semen@yahoo.com.
authors.forename: Khrystyna
authors.initials: K
authors.lastname: Semen
authors.affiliation: Department of Histology, Cytology and Embryology, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine. Electronic address: yelisol@gmail.com.
authors.forename: Olha
authors.initials: O
authors.lastname: Yelisyeyeva
authors.affiliation: Department of Analytical Chemistry, Medical University of Bialystok, Jana Kilinskego 1, 15089 Bialystok, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Jarocka-Karpowicz
authors.affiliation: Department of Pharmaceutical, Organic, and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine.
authors.forename: Danylo
authors.initials: D
authors.lastname: Kaminskyy
authors.affiliation: Lviv Regional Clinical Hospital, Chernigivska 7, 79010 Lviv, Ukraine.
authors.forename: Lyubomyr
authors.initials: L
authors.lastname: Solovey
authors.affiliation: Department of Analytical Chemistry, Medical University of Bialystok, Jana Kilinskego 1, 15089 Bialystok, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Skrzydlewska
authors.affiliation: Department of Propedeutics of Internal Medicine #2, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine.
authors.forename: Ostap
authors.initials: O
authors.lastname: Yavorskyi
mesh_terms: D000328:Adult; D000447:Aldehydes / Q000032:analysis*; D005227:Fatty Acids / Q000032:analysis*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D000068677:Sildenafil Citrate / Q000008:administration & dosage* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000447:Aldehydes; D005227:Fatty Acids; C462359:tert-4-hydroxy-2-nonenal; D009569:Nitric Oxide; D000068677:Sildenafil Citrate
keywords: Fatty acid composition; Heart rate variability; Hydroxynonenal; Oxidative stress; Pulmonary arterial hypertension; Sildenafil