Cardiorespiratory effects induced by 2-nitrate-1,3-dibuthoxypropan are reduced by nitric oxide scavenger in rats

Auton Neurosci. 2014 Apr:181:31-6. doi: 10.1016/j.autneu.2013.12.012. Epub 2013 Dec 24.

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.

Keywords: Arterial pressure; Nitric oxide; Organic nitrate; Respiratory rate.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Arterial Pressure / drug effects*
  • Arterial Pressure / physiology
  • Bradycardia / chemically induced
  • Bradycardia / drug therapy
  • Bradycardia / physiopathology
  • Cardiovascular Agents / administration & dosage
  • Cardiovascular Agents / pharmacology*
  • Consciousness
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects*
  • Heart Rate / physiology
  • Hydroxocobalamin / pharmacology
  • Hypotension / chemically induced
  • Hypotension / drug therapy
  • Hypotension / physiopathology
  • Male
  • Nitrates / administration & dosage
  • Nitrates / pharmacology*
  • Nitric Oxide / metabolism
  • Nitroglycerin / administration & dosage
  • Nitroglycerin / pharmacology
  • Propane / administration & dosage
  • Propane / analogs & derivatives*
  • Propane / pharmacology
  • Rats
  • Rats, Wistar
  • Respiration / drug effects*
  • Tachypnea / chemically induced
  • Tachypnea / drug therapy
  • Tachypnea / physiopathology
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / pharmacology

Substances

  • 2-nitrate-1,3-dibuthoxypropan
  • Cardiovascular Agents
  • Nitrates
  • Vasodilator Agents
  • Nitric Oxide
  • Nitroglycerin
  • Hydroxocobalamin
  • Propane