Effect of the S-nitrosoglutathione reductase inhibitor N6022 on bronchial hyperreactivity in asthma.

ABSTRACT:

Rationale

Patients with asthma demonstrate depletion of the endogenous bronchodilator GSNO and upregulation of GSNOR.

Objectives

An exploratory proof of concept clinical study of N6022 in mild asthma to determine the potential bronchoprotective effects of GSNOR inhibition. Mechanistic studies aimed to provide translational evidence of effect.

Methods

Fourteen mild asthma patients were treated with intravenous N6022 (5 mg) or placebo and observed for 7 days, with repeated assessments of the provocative dose of methacholine causing a 20% fall in FEV1 (methacholine PC₂₀ FEV1), followed by a washout period and crossover treatment and observation. In vitro studies in isolated eosinophils investigated the effect of GSNO and N6022 on apoptosis.

Measurements and

SUBMITTER: Que LG 

PROVIDER: S-EPMC5946144 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature