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(A) Pravastatin had no statistically significant effect on methacholine (MCh)-induced airway hyperreactivity (AHR) except at the 0.5?mg/mL MCh dose (*P?[http://www.selleckchem.com/products/ipi-145-ink1197.html this website] Of note, the horizontal dotted line in Fig.?Fig.4B4B represents the expected Rrs for FA controls in our mouse model; it represents a historical average of data from multiple prior experiments using our model system and provides a reference point for the expected Rrs in FA mice. To measure pravastatin-dependent changes in AHS, we used the provocative concentrations (PC) of MCh (0.5, 1.0, and 2.0?mg/mL) to cause a 5, 10, and 20% increase [http://en.wikipedia.org/wiki/Alkaline_phosphatase (-)-p-Bromotetramisole Oxalate] from baseline Rrs (PC5, PC10, and PC20, respectively), representing low, medium, and high MCh doses in our model system (Fig.?(Fig.4C).4C). We used this percentage range because of the constraints of our plethysmograph system in terms of the achievable Rrs using only three doses of MCh: 0.5, 1.0, and 2.0?mg/mL. For the OVA groups, saline challenge (0?mg/mL MCh) followed by these three doses of MCh increased average Rrs above baseline values by a maximum of 18.5 to 22% at the 2.0?mg/mL dose. For the FA groups, this increase ranged from 5.4 to 8.3% at the 2.0?mg/mL MCh dose. We determined that PC5, PC10, and PC20 was an appropriate range [http://www.selleckchem.com/products/JNJ-26481585.html Epigenetics inhibitor] of % increase in Rrs fitting our model system, where PC10 is approximately half of the increase in Rrs values above baseline. Therefore, within the constraints of our model, PC10 and the range we chose (PC5 to PC20) is a meaningful measure. The MCh provocative concentrations were higher for pravastatin- than PBS-treated OVA mice for PC10 (*P?=?0.04) and PC20 (**P?=?0.024 by Wilcoxon signed rank test). For PC10 and PC20 challenges, it takes twice the dose of MCh to induce an equivalent % increase in Rrs in the pravastatin-treated mice as compared to PBS controls. Therefore, treatment with i.t. pravastatin significantly decreased AHS at the medium and high PC doses in OVA-exposed mice. There were no significant differences in the FA groups (P?=?NS, Fig.?Fig.4C4C). In our mouse model, OVA exposure decreases Cdyn due to increased airway inflammation, edema, and mucus production. As expected, OVA sensitization and exposure decreased Cdyn relative to FA controls (OVA + i.t. PBS vs. FA + i.t. PBS, P?