title: Cardiorespiratory effects induced by 2-nitrate-1,3-dibuthoxypropan are reduced by nitric oxide scavenger in rats.
abstract: The search for new nitric oxide donors is warranted by the limitations of organic nitrates currently used in cardiology. The new organic nitrate 2-nitrate-1,3-dibuthoxypropan (NDBP) exhibited promising cardiovascular activities in previous studies. The aim of this study was to investigate the cardiorespiratory responses evoked by NDBP and to compare them to the clinically used organic nitrate nitroglycerine (NTG). Arterial pressure, heart rate and respiration were recorded in conscious adult male Wistar rats. Bolus i.v. injection of NDBP (1 to 15mg/kg; n=8) and NTG (0.1 to 5mg/kg; n=8) produced hypotension. NDBP induced bradycardia at all doses, while NTG induced tachycardia at three lower doses but bradycardia at higher doses. Hydroxocobalamin (20mg/kg; HDX), a NO scavenger, blunted hypotension induced by NDBP (15mg/kg), and its bradycardic effect (n=6). In addition, HDX blunted both hypotension and bradycardia induced by a single dose of NTG (2.5mg/kg; n=6). Both NDBP and NTG altered respiratory rate, inducing a biphasic effect with a bradypnea followed by a tachypnea; HDX attenuated these responses. Our data indicate that NDBP and NTG induce hypotension, bradycardia and bradypnea, which are mediated by nitric oxide release.
authors.affiliation: Biotechnology Center, Federal University of Paraiba, João Pessoa, PB, Brazil.
authors.forename: Thyago M
authors.initials: TM
authors.lastname: Queiroz
authors.affiliation: Biotechnology Center, Federal University of Paraiba, João Pessoa, PB, Brazil.
authors.forename: Leônidas G
authors.initials: LG
authors.lastname: Mendes-Júnior
authors.affiliation: Biotechnology Center, Federal University of Paraiba, João Pessoa, PB, Brazil.
authors.forename: Drielle D
authors.initials: DD
authors.lastname: Guimarães
authors.affiliation: Biotechnology Center, Federal University of Paraiba, João Pessoa, PB, Brazil.
authors.forename: Maria S
authors.initials: MS
authors.lastname: França-Silva
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, NSW, Australia. Electronic address: Eugene.nalivaiko@newcastle.edu.au.
authors.forename: Eugene
authors.initials: E
authors.lastname: Nalivaiko
authors.affiliation: Biotechnology Center, Federal University of Paraiba, João Pessoa, PB, Brazil.
authors.forename: Valdir A
authors.initials: VA
authors.lastname: Braga
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects* / Q000502:physiology; D001919:Bradycardia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006879:Hydroxocobalamin / Q000494:pharmacology; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009566:Nitrates / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology; D011407:Propane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects*; D059246:Tachypnea / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: C576760:2-nitrate-1,3-dibuthoxypropan; D002317:Cardiovascular Agents; D009566:Nitrates; D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin; D006879:Hydroxocobalamin; D011407:Propane
keywords: Arterial pressure; Nitric oxide; Organic nitrate; Respiratory rate