Cigarette‐smoke‐dependent changes in the respiratory and cardiovascular system of spontaneously hypertensive (SH) rats and the effect of smoking cessation

      Berges, A.; Friedrichs, B.; Gallitz, I.; Quadt-Humme, S.; Steffen, Y.; Stolle, K.; Lebrun, S.; Lietz, M.
      Conference date
      Mar 6, 2011
      Conference name
      Society of Toxicology (SOT) 2011

      Previously, we have shown that cigarette smoke affects cardiac function, hypertrophy status, and serum proteins in SH rats (abstract 912; 48th Annual Meeting & ToxExpoTM [2009]). Here, we investigate the reversibility of these effects after smoking cessation (SC). SH rats were exposed to diluted cigarette mainstream smoke (MS) from the reference cigarette 3R4F (MS-only; 900 µg total particulate matter/day; 5 days/week) or to fresh air (SHAM) for 90 days. SC experiments covered exposure for 30 days MS + 60 days SHAM (SC-1) and 60 days MS + 30 days SHAM (SC-2). Endpoints tested were body weight, heart hypertrophy status, neutrophils in bronchioalveolar lavage fluid, expression levels of matrix metalloproteinase-1 (MMP-1) and metallopeptidase inhibitor-1 (TIMP-1). At 90 days, parameters were decreased (body weight) or increased (all other endpoints) in the MS-only group compared to both cessations groups, which, importantly, display a SHAM-like phenotype: body weight [g]: 275.9+16.8 (MS-only), 316.0±18.5 (SC-1), 311.8+19.6 (SC-2), 301.7±28.7 (SHAM); hypertrophy status [left ventricle weight (g)/tibia length (mm)]: 0.023±0.002 (MS-only), 0.020±0.001 (SC-1), 0.021±0.001 (SC-2), 0.019±0.002 (SHAM); TIMP-1 [pg/ml]: 1990.0±219.6 (MS-only), 247.0±12.4 (SC-1), 234.7±11.5 (SC-2), 270.6±19.7 (SHAM); MMP-1 [ng/ml]: 7.3±0.4 (MS-only), 3.2±0.4 (SC-1), 3.0±0.4 (SC-2), 3.8±0.6 (SHAM); neutrophil count [%]: 12.7±1.1 (MS-only), 0.7±0.1 (SC-1), 3.6±0.6 (SC-2), 0.4±0.1 (SHAM). Further endpoints are currently under investigation. Hence, this experimental format may turn out to be suitable to evaluate respiratory and cardiovascular effects of potentially reduced-risk tobacco products.