Effects of salbutamol and Ro-20-1724 on airway and parenchymal mechanics in rats

J Appl Physiol (1985). 1999 Oct;87(4):1373-80. doi: 10.1152/jappl.1999.87.4.1373.

Abstract

We investigated the effects of a selective beta(2)-agonist, salbutamol, and of phosphodiesterase type 4 inhibition with 4-(3-butoxy-4-methoxy benzyl)-2-imidazolidinone (Ro-20-1724) on the airway and parenchymal mechanics during steady-state constriction induced by MCh administered as an aerosol or intravenously (iv). The wave-tube technique was used to measure the lung input impedance (ZL) between 0.5 and 20 Hz in 31 anesthetized, paralyzed, open-chest adult Brown Norway rats. To separate the airway and parenchymal responses, a model containing an airway resistance (Raw) and inertance (Iaw), and a parenchymal damping (G) and elastance (H), was fitted to ZL spectra under control conditions, during steady-state constriction, and after either salbutamol or Ro-20-1724 delivery. In the Brown Norway rat, the response to iv MCh infusion was seen in Raw and G, whereas continuous aerosolized MCh challenge produced increases in G and H only. Both salbutamol, administered either as an aerosol or iv, and Ro-20-1724 significantly reversed the increases in Raw and G when MCh was administered iv. During the MCh aerosol challenge, Ro-20-1724 significantly reversed the increases in G and H, whereas salbutamol had no effect. These results suggest that, after MCh-induced changes in lung function, salbutamol increases the airway caliber. Ro-20-1724 is effective in reversing the airway narrowings, and it may also decrease the parenchymal constriction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / pharmacology*
  • Adrenergic beta-Agonists / pharmacology*
  • Airway Resistance / drug effects*
  • Albuterol / pharmacology*
  • Animals
  • Bronchodilator Agents / pharmacology*
  • Lung / drug effects*
  • Lung / physiology*
  • Male
  • Methacholine Chloride / pharmacology
  • Phosphodiesterase Inhibitors / pharmacology*
  • Rats
  • Rats, Inbred BN
  • Respiratory Mechanics / drug effects*

Substances

  • Adrenergic beta-Agonists
  • Bronchodilator Agents
  • Phosphodiesterase Inhibitors
  • Methacholine Chloride
  • 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
  • Albuterol