EFFECT OF INHALED ATRIAL-NATRIURETIC-PEPTIDE AND A NEUTRAL ENDOPEPTIDASE INHIBITOR ON HISTAMINE-INDUCED BRONCHOCONSTRICTION

The reduced ability of inhaled compared with intravenous atrial natriu retic peptide (ANP) to modify bronchial reactivity and tone may be due to degradation of the peptide by neutral endopeptidase (NEP) within t he airways. To test this hypothesis, we have examined the effect of th iorphan, an NEP inhibitor, on the protection afforded by inhaled ANP a gainst histamine-induced bronchoconstriction in 10 mildly asthmatic pa tients. Pretreatment with ANP alone attenuated the bronchoconstrictor response to histamine with a mean (SEM) maximum percent fall in FEV(1) 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 inh alation 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 th e guanylyl cyclase pathway, by which ANP acts, in the treatment of ast hma by the administration of ANP analogues stable to neutral endopepti dase.