title: Long-acting phosphodiesterase 5 inhibitor, tadalafil, and superoxide dismutase mimetic, tempol, protect against acute hypoxia-induced pulmonary hypertension in rats.
abstract: Long-acting phosphodiesterase 5 (PDE5) inhibitor, tadalafil, was recently approved for the treatment of pulmonary hypertension. Apart from being a PDE5 inhibitor, tadalafil also possesses antioxidant activity. The aim of this study was to probe whether tadalafil has any beneficial effect over tempol owing to its antioxidant action in addition to PDE5 inhibitory activity. Albino Wistar rats were pretreated with tadalafil (10 mg/kg) or vehicle 2 h before hypoxic exposure, whereas tempol (20 mg/kg) was given 5 min before induction of hypoxia. Right ventricular systolic pressure (RVSP), mean arterial pressure (MAP), heart rate (HR), right ventricular contractility (RVdP/dtmax) and cardiac output (CO) were recorded while subjecting rats to acute hypoxia for 30 min. Lipid peroxidation and reduced glutathione were estimated in serum before and after hypoxia exposure. Tadalafil as well as tempol significantly prevented hypoxia-induced rise in RVSP (p < 0.001) and RVdP/dtmax (p < 0.05). Both tadalafil and tempol pretreatment partially prevented (p < 0.01) the rise in CO due to hypoxia. Tadalafil did not produce any significant change in MAP, whereas tempol led to a significant fall (p < 0.01) in MAP. Acute hypoxia increased the oxidative stress levels. Tadalafil pretreatment partially prevented hypoxia-induced oxidative stress, while tempol pretreatment completely prevented hypoxia-induced oxidative stress. Results suggest that tadalafil because of its antioxidant action in addition to PDE5 inhibitory activity is more appropriate for the prevention of hypoxic pulmonary hypertension than tempol. Tempol also produced undesirable systemic hypotension as side effect, which was not seen with tadalafil because of its pulmonary selective action.
authors.affiliation: Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India. masratrashid1@gmail.com
authors.forename: M
authors.initials: M
authors.lastname: Rashid
authors.forename: A
authors.initials: A
authors.lastname: Kotwani
authors.forename: M
authors.initials: M
authors.lastname: Fahim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology / Q000627:therapeutic use*; D002302:Cardiac Output / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels; D000068581:Tadalafil; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D002243:Carbolines; D003497:Cyclic N-Oxides; D058986:Phosphodiesterase 5 Inhibitors; D013113:Spin Labels; D008315:Malondialdehyde; D000068581:Tadalafil; C001803:tempol