VIP AND NITRIC-OXIDE - PHYSIOLOGICAL COTRANSMITTERS WITH ANTAGONISTIC ROLES IN INFLAMMATION

As Physiological co-transmitters, vasoactive intestinal peptide (VIP) and nitric oxide (NO), constitutively produced in low concentrations, interact in several ways: 1) VIP and NO synthase co-exist in some of the same neurons, e.g., in myenteric plexus and tracheal ganglia; 2) both transmitters are released during NANC relaxation of gastrointestinal and airway smooth muscle, simulated by electrical field stimulation; and 3) in some tissues, e,g., guinea pig gastric fundus, VIP stimulates NO release and NO promotes VIP release, while in other tissues, e.g., guinea pig trachea, VIP-induced relaxation appears to be independent of NO release. Released together, either independently or interdependently, VIP and NO cooperatively mediate smooth muscle relaxation (and other functions) via two separate but complementary pathways, the stimulation of adenylyl cyclase and of guanylyl cyclase, respectively. In the setting of acute tissue injury, however, VIP and NO have opposing roles. VIP prevents of attenuates acute lung injury in a variety of experimental models, while excess NO, acting directly or with other free radicals, may be an essential intermediary in the production of lung injury in at least two models of oxidant stress. Under such conditions, therefore, VIP acts to protect the lung and probably other tissues and organs against inflammatory injury, whereas excess NO promotes that injury.