VIRAL RESPIRATORY-INFECTION CAUSES AIRWAY HYPERRESPONSIVENESS AND DECREASES HISTAMINE N-METHYLTRANSFERASE ACTIVITY IN GUINEA-PIGS

We investigated the effects of viral respiratory infection by Sendai v irus on bronchial responses to aerosolized histamine in anesthetized g uinea pigs and on the activity of histamine N-methyltransferase (HMT). We measured the change in total pulmonary resistance induced by hista mine in the presence or absence of a specific HMT inhibitor, SKF 91488 , in noninfected and infected animals. In the absence of SKF 91488, th e bronchoconstrictor response to histamine was greater in infected tha n in noninfected animals. SKF 91488 (10(-2) M, 90 breaths) potentiated the responses to histamine in noninfected animals, and the magnitude of augmented responses to histamine by SKF 91488 was similar to that b y viral infection. Furthermore, SKF 91488 did not further potentiate t he responses to histamine in infected animals. However, responses to a erosolized acetylcholine were unaffected by viral infection and SKF 91 488. The HMT activity decreased by 56% in the trachea, 86% in the bron chi, and 52% in the parenchymal tissue in the infected animals. In con trast to HMT activity, acetylcholinesterase activity was unaffected by viral infection. These results suggest that respiratory infection by Sendai virus causes enhanced bronchial responsiveness to histamine by decreasing HMT activity in airways.