Effects of salbutamol and Ro-20-1724 on airway and parenchymal mechanics in rats.
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.
Peták
F
F
Division of Clinical Sciences, Institute for Child Health Research, Perth, Western Australia 6001. petak@dmi.szote.u-szeged.hu
Wale
J L
JL
Sly
P D
PD
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D015656:Respiratory Mechanics / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D010726:Phosphodiesterase Inhibitors; D016210:Methacholine Chloride; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D000420:Albuterol