Potent bronchodilation and reduced stiffness by relaxant stimuli under dynamic conditions

¹ Discipline of Physiology, School of Biomedical, Biomolecular and Chemical Sciences and Discipline of Pharmacology, School of Medicine and Pharmacology, University of Western Australia

	Abstract

Airway relaxation to isoprenaline, sodium nitroprusside (SNP) and electrical field stimulation (EFS) was compared under static and dynamic conditions. The capacity of relaxants to reduce airway stiffness and thus potentially contribute to bronchodilation was also investigated.

Relaxation responses were recorded in fluid filled bronchial segments from pigs under static conditions and during volume oscillations simulating tidal and twice tidal manoeuvres. Bronchodilation was assessed from the reduction in carbachol-induced lumen pressure, at isovolume points in pressure cycles produced by volume oscillation, and stiffness was assessed from cycle amplitudes.

Under static conditions all three inhibitory stimuli produced partial relaxation of carbachol-induced contraction. Volume oscillation alone also reduced contraction in an amplitude-dependent manner. However maximum relaxation was observed when isoprenaline or SNP were combined with volume oscillation, virtually abolishing contraction at the highest drug concentrations. The proportional effects of isoprenaline and EFS were not different under static or oscillating conditions, whereas relaxation to SNP was slightly greater in oscillating airways. All three inhibitory stimuli also strongly reduced carbachol-induced airway stiffening.

We conclude that bronchoconstriction is strongly suppressed by combining inhibitory stimulation of ASM with cyclical mechanical strains. The capacity of ASM relaxants to also reduce stiffness may further contribute to bronchodilation.