Influence of Elevated Plasma Levels of Atrial Natriuretic Factor on Bronchial Reactivity in Asthma

Abstract

Recent studies have demonstrated that elevation of plasma atrial natriuretic factor (ANF) levels may produce significant bronchodilation in the constricted asthmatic airway. The current study was designed to examine the effect of both physiologic and pharmacologic plasma levels of ANF on bronchial reactivity to histamine in asthmatic subjects. A total of eight atopic men with well-controlled asthma were studied, mean (SD) FEV1 3.50 (0.73) L, equivalent to 87 (11)% of predicted; bronchial reactivity as measured by histamine PC20 was 0.77 mg/ml (geometric mean). On four separate study days infusions of 1, 3, or 10 pmol/kg/min of ANF or placebo were administered in a double-blind, randomized manner. Once steady-state plasma levels had been achieved, measurement of bronchial reactivity was repeated. Mean (SEM) basal ANF level was 18.5 (3.5) pg/ml and rose to 41 (4.3), 157 (15), and 500 (30) pg/ml with increasing doses of ANF. With placebo infusion geometric mean histamine PC20 was 0.77 mg/ml and rose to 1.15 mg/ml (p less than 0.05), 1.90 mg/ml (p less than 0.001), and 3.38 mg/ml (p less than 0.001), corresponding to a 1.5-, 2.5-, and 4.4-fold protection with respective ANF infusions. There was no significant change in plasma epinephrine. These results show that at both physiologic and pathophysiologic plasma levels ANF may significantly decrease bronchial reactivity to histamine in asthma.