Bronchial circulatory reversal of methacholine-induced airway constriction

Although a role for the bronchial circulation in clearance of bronchoactive agents has been frequently proposed, experimental evidence is limited. In this study, we determined the importance of bronchial blood flow (Q̇(BA)) in the recovery from methacholine-(MCh) induced bronchoconstriction. In 10 pentobarbital-anesthetized ventilated sheep, the bronchial branch of the bronchoesophageal artery was cannulated and perfused (0.7 ml·min^-1·kg^-1) with blood pumped from the femoral artery. MCh was infused directly into the bronchial artery at increasing concentrations (10^-7 to 10^-5 M). MCh infusion caused a concentration-dependent increase in airway resistance at constant Q̇(BA). However, the time constant of recovery (TC) from airway constriction after cessation of the MCh infusion was not dependent on the MCh concentration or the magnitude of the increases in airway resistance. When Q̇(BA) was at 50, 100, and 200% of control level, with constant MCh concentration, TC was 44 ± 6, 25 ± 2, and 24 ± 2 (SE) s at each flow level, respectively. TC at 50% of control Q̇(BA) was significantly greater than at control Q̇(BA) (P < 0.01). Thus the magnitude of Q̇(BA) can alter the time course of recovery from MCh-induced increases in airway resistance. These results document the importance of Q̇(BA) in reversing agonist-induced constriction and suggest that an impaired bronchial circulation may contribute to the mechanism of airway hyperreactivity.