tetrodotoxin and Bronchial-Spasm

To further examine the role that substance P plays in initiating the observed massive postmortem bronchoconstriction in guinea pig lungs and to explore the role of neural reflex in this airway spasm, six groups of animals were employed: control (n = 6), morphine (n = 6), substance P (n = 5), chronic capsaicin pretreatment + substance P (n = 5), tetrodotoxin (TTX) + acute capsaicin (n = 4), and chlorisondamine + acute capsaicin (n = 5). Pressure-volume curves were performed prior to and following the initiation of artificial pulmonary perfusion with 1% bovine serum albumin and 5% dextran in Tyrode's solution. A decrease in inflation volume (the lung volume between transpulmonary pressure of 0 and 30 cmH2O during inflation) was used as an index of bronchoconstriction. In control animals, inflation volume decreased to 20-30% of the base-line value at 15-30 min of perfusion, indicating massive bronchial constriction during this time period. Morphine (an agent inhibiting substance P release) significantly attenuated the spasm, whereas the presence of substance P in the perfusate markedly enhanced the constriction. Depletion of endogenous substance P by chronic capsaicin pretreatment did not affect exogenous substance P-induced spasm. Acute capsaicin-induced bronchoconstriction was significantly attenuated by TTX but was not affected by the ganglionic blocking agent, chlorisondamine. These data suggest that substance P initiates the massive postmortem bronchoconstriction in guinea pig lungs and that substance P is released by local stimulation of sensory nerve endings via axonal reflex.

Topics: Animals; Bronchial Spasm; Capsaicin; Chlorisondamine; Guinea Pigs; Male; Postmortem Changes; Substance P; Tetrodotoxin; Total Lung Capacity; Vital Capacity