Am. J. Respir. Crit. Care Med., Vol 151, No. 6, Jun 1995, 2003-2005.
Effect of inhaled atrial natriuretic peptide and a neutral endopeptidase inhibitor on histamine-induced bronchoconstriction
RM Angus, EA Millar, GW Chalmers and NC Thomson
Department of Respiratory Medicine, Western Infirmary, Glasgow, United Kingdom.
The reduced ability of inhaled compared with intravenous atrial natriuretic
peptide (ANP) to modify bronchial reactivity and tone may be due to
degradation of the peptide by neutral endopeptidase (NEP) within the
airways. To test this hypothesis, we have examined the effect of thiorphan,
an NEP inhibitor, on the protection afforded by inhaled ANP against
histamine-induced bronchoconstriction in 10 mildly asthmatic patients.
Pretreatment with ANP alone attenuated the bronchoconstrictor response to
histamine with a mean (SEM) maximum percent fall in FEV1 after histamine of
15.9 (2.9) (p < 0.05) compared with 24 (2.9) after placebo and 24 (4)
after pretreatment with thiorphan alone. Prior inhalation of thiorphan
greatly enhanced the ANP effect: the mean maximum percent fall after this
combination was 5.1 (2.3) (p < 0.01, compared with ANP alone). Our
results suggest that airway NEP is important in modulating the effect of
inhaled ANP. It may be possible to exploit the guanylyl cyclase pathway, by
which ANP acts, in the treatment of asthma by the administration of ANP
analogues stable to neutral endopeptidase.
