The effects of alpha 2-adrenergic agonism with clonidine on the pulmonary and collateral resistances in the canine lung challenged with histamine.

In anesthetized dogs, we studied the effects of colonidine on the changes in pulmonary collateral resistance in response to histamine challenge. In the whole lung, an intravenous histamine increased the inspiratory (Ri), and expiratory (Re) resistance by 142 +/- 12%, and 229 +/- 30% over the control, respectively. Pretreatment with clonidine (0.05 mg/kg, iv) significantly attenuated the increases to 76 +/- 16% (Ri), and 114 +/- 22% (Re) (p less than 0.05). However, the responses to histamine were restored after an addition of yohimbine (0.15 mg/kg, iv) before clonidine. A bronchoscope wedge technique was used to measure the collateral resistance (Rcs) in the lung periphery. Histamine was administered in aerosolized form to a wedged sublobar segment. The local histamine challenge significantly increased Rcs. Pretreatment with clonidine did not discernibly affect the histamine-induced increase in Rcs. On the other hand, pretreatment with isoproterenol (0.02 mg/kg, iv) remarkably attenuated the Rcs response to histamine. The results indicate that alpha 2-adrenergic agonism with clonidine inhibits the bronchoconstriction induced by histamine. alpha 2- antagonism with yohimbine abolishes the antiasthmatic effect of clonidine. In the lung periphery, the Rcs response to histamine is not altered by alpha 2, but by beta 2 adrenergic agonism with isoproterenol.