Homeostatic regulation of bronchomotor tone by sympathetic activation during bronchoconstriction in normal and...

It has been assumed previously that the sympathetic nervous system (SNS) serves to antagonize bronchoconstrictor stimuli. To assess the homeostatic regulatory effect elicited by exogenously induced bronchoconstriction, we studied the effect of inhaled methacholine on the SNS response in 12 normal and 9 asthmatic humans. Exogenous SNS response was assessed as change in plasma epinephrine and norepinephrine concentrations from basal levels during inhalation challenge. A 74 +/- 3% decrease in specific airway conductance (SGaw) (p less than 0.001) was induced in normal subjects and a 78 +/- 7% decrease in asthmatics by methacholine challenge (p less than 0.001). Neither plasma epinephrine nor norepinephrine increased significantly from basal concentrations in normal or asthmatic subjects after maximal challenge (p greater than 0.33). To determine if physiologically achievable epinephrine concentrations potentially could modulate bronchoconstriction, the effect of intravenously infused epinephrine was measured in 11 of these subjects. After the highest dose of methacholine, a 15-min intravenous infusion of epinephrine (0.06 micrograms/kg/min) caused an 85 +/- 7% increase in SGaw in normal subjects (p less than 0.02). In asthmatics, a 319 +/- 68% increase in SGaw (p less than 0.002) was observed with similar changes in plasma epinephrine. Plasma epinephrine concentrations after infusion were comparable to those obtained in 4 normal and 1 asthmatic subject undergoing 60-degree, head-up tilt 1 h after volume depletion with intravenously administered furosemide. We conclude that physiologic concentrations of epinephrine can modulate moderately severe bronchoconstriction. However, the SNS does not regulate bronchomotor tone during mild to moderate bronchoconstriction.