Additive Effect of Nitroglycerine Inhalation on β2-agonist-Induced Bronchodilatation in Asthmatics

Abstract

Summary: The current treatment of airway obstruction using β-agonists and theophylline is designed to increase intracellular level of cAMP. Experimental data show that cGMP and cAMP induce functionally additive relaxation of airways. Nitrates relax smooth muscle through the activation of guanylate cyclase. We wondered whether an additive effect of nitroglycerin (NTG) on β₂-agonist-induced bronchodilatation was present in asthmatic patients.

To this aim we evaluated the acute bronchodilating effect of inhaled salbutamol (200 μg MDI) in 10 asthmatics, pre-treated with inhaled NTG or placebo, in a double-blind cross-over design. FEV₁ after NTG was higher than that obtained after placebo (2197±175 vs. 1981±155 ml, P<0.001). Mean FEV₁ obtained 5 min after salbutamol was higher when patients were pre-treated with NTG than placebo (2694±217 vs. 2440±228 ml respectively, P<0.001). The bronchodilatation due to salbutamol was identical whether NTG or placebo was inhaled first, respectively at 458±68 and 497±44 ml after 5 min. After 15 min FEV₁ was higher than baseline, but no significant difference was still present between the value observed after pre-treatment with NTG or placebo (2554±235 and 2551±205 ml respectively).

In conclusion, in asthmatics nebulized NTG produces a moderate and short-lasting bronchodilatation, which is additive with that produced by salbutamol.