We studied the effects on
ozone-induced airway hyperreactivity of
U-60,257, a pyrroloprostacyclin shown to inhibit
leukotriene C/D biosynthesis in vitro. A group of 5 guinea pigs were pretreated with
U-60,257 (5 mg/kg IV), and studied before and 30 min after a 15 min exposure to 3.0 ppm
ozone. These animals were compared to a similarly exposed group that was untreated (n = 10). Reactivity was determined by measuring specific airway resistance (SRaw) upon intravenous
acetylcholine infusion in unanesthetized, spontaneously breathing animals. Prior to
ozone exposure, we found that
U-60,257 treatment did not affect either SRaw or
muscarinic reactivity. After exposure to 3.0 ppm, all untreated guinea pigs showed substantial
muscarinic hyperreactivity. In contrast, no significant change in SRaw or
muscarinic reactivity occurred after
ozone in any animal pretreated with
U-60,257. We conclude that
ozone-induced
bronchial hyperreactivity in the guinea pig rapidly develops after a brief, high level exposure. This effect may be mediated, in part, by
leukotrienes generated upon
ozone exposure.