Time course of histamine-induced bronchoconstriction and its adrenergic and H2 modulation

We characterized the complete time course of histamine-induced bronchoconstriction and its modulation via the release of endogenous catecholamines and by its actions on H2-receptors in anesthetized, tracheostomized, paralyzed, and artificially ventilated mongrel dogs. Respiratory resistance (R) and elastance (E) were estimated continuously with a recursive least squares estimator. Three protocols were followed in which multiple histamine bolus injections were given 1 h apart. We found that the time courses of E and R had consistent patterns (transient peak that returned to baseline within 1000 sec) even in cases of low mean arterial pressure (MAP). Indomethacin pre-treatments prevented tachyphylaxis to repeated i.v. challenges. beta-blockade produced a mild increase in baseline and a potentiation of the histamine-induced response in E and these effects were not altered with further alpha-or H2-blockade. Blockade of alpha-receptors increased the time to recovery in both E and MAP presumably by decreasing blood flow. Finally, we suggest that preventing the H2-receptor induced increase in bronchial blood flow may have increased the time to maximal E without affecting the recovery time.