Long Term Cigarette Smoke Exposure Does Not Increase Airway Responsiveness in Rats

Abstract

To ascertain whether chronic cigarette smoke exposure induces increased airway responsiveness, we performed methacholine response tests in Sprague-Dawley rats by calculating pulmonary resistance after nebulization of saline followed by an increasing concentration of methacholine. We also calculated the concentration of methacholine which doubled the baseline resistance (R200). Tests were performed at baseline and after 2, 4, 8, and 12 months of exposure to the smoke of seven cigarettes per day, 5 days each week; control animals were exposed to room air. At the completion of the study, there were 13 rats in the smoke-exposed group and 7 rats remaining in the control group. Airway morphology was assessed using a point counting technique. We found that (1) chronic exposure to cigarette smoke did not alter either the baseline resistance or the R200; (2) the saline baseline resistance decreased over time in the control animals; and (3) at the 12-month time point, smokers with increased baseline airway resistance had greater amounts of airway smooth muscle compared with the smoke-exposed animals without increased resistance. We conclude that in this animal model, long term exposure to cigarette smoke did not alter the response to methacholine but did increase airway smooth muscle and baseline resistance in some but not all animals.

Involvement of IL-13 in Tobacco Smoke–Induced Changes in the Structure and Function of Rat Intrapulmonary Airways

“…In a previous study, where no significant difference in AHR was seen after 12 months of TS exposure, airways with increased baseline airway resistance had greater amounts of ASM compared with TSexposed animals without increased resistance (11), suggesting the two features are linked. An increase in SMA suggests an increase in smooth muscle cells; however, SMA is also found in noncontractile fibroblasts (34), and a functional contribution from this cell type cannot be ruled out on the basis of the current studies.…”

“…After 15 weeks of TS exposure (three cigarettes per day; 5 d/wk), Xu and colleagues demonstrated AHR in Long Evans rats (10). Wright and colleagues lengthened the exposure time to 12 months (seven cigarettes per day; 5 d/wk) and did not see a difference in the baseline resistance or methacholine sensitivity (R 200 ) of Sprague-Dawley rats (11). Some of these discrepancies might be due to strain differences in sensitivity to TS, length of exposures, or types of cigarettes used.…”

“…In one such study, a modest increase in procollagen gene expression in the small airway walls of rats exposed to TS was reported (8). In addition, these models have focused on studying the effects of TS exposure on large airway structure and function (7)(8)(9)(10)(11)(12).…”