METHACHOLINE-INDUCED BRONCHOCONSTRICTION IN RATS - EFFECTS OF INTRAVENOUS VS AEROSOL DELIVERY

To determine the predominant site of action of methacholine (MCh) on l ung mechanics, two groups of open-chest Sprague-Dawley rats were studi ed. Five rats were measured during intravenous infusion of MCh (iv gro up), with doubling of concentrations from 1 to 16 mu g.kg(-1).min(-1). Seven rats were measured after aerosol administration of MCh with dos es doubled from 1 to 16 mg/ml (ae group). Pulmonary input impedance (Z L) between 0.5 and 21 Hz was determined by using a wave-tube technique . A model containing airway resistance (Raw) and inertance (Iaw) and p arenchymal damping (G) and elastance (H) was fitted to the ZL spectra. In the iv group, MCh induced dose-dependent increases in Raw [peak re sponse 270 +/- 9 (SE) % of the control level; P < 0.05] and in G (340 +/- 150%; P < 0.05), with no increase in law (30 +/- 59%) or H (111 +/ - 9%). In the ae group, the dose-dependent increases in Raw (191 +/- 1 4%; P < 0.05) and G (385 +/- 35%; P < 0.05) were associated with a sig nificant increase in H (202 +/- 8%; P < 0.05). Measurements with diffe rent resident gases [air vs. neonoxygen mixture, as suggested (K. R. L utchen, Z. Hantos, F. Petak, A. Adamicza, and B. Suki. J. Appl. Physio l. 80: 1841-1849, 1996)] in the control and constricted states in anot her group of rats suggested that the entire increase seen in G during the iv challenge was due to ventilation inhomogeneity, whereas the ae challenge might also have involved real tissue contractions via select ive stimulation of the muscarinic receptors.