Whole body plethysmography reveals differential ventilatory responses to ozone in rat models of cardiovascular disease

Abstract

To elucidate key factors of host susceptibility to air pollution, healthy and cardiovascular (CV)-compromised rats were exposed to air or ozone (O₃) at 0.25, 0.5, or 1.0 ppm for 4 h. We hypothesized that rat strains with the least cardiac reserve would be most prone to develop significant health effects. Using flow whole body plethysmography (FWBP), ventilatory responses in healthy 3-month-old male rats [i.e. Wistar–Kyoto (WKY), Wistar (WIS), and Sprague–Dawley (SD) strains] were compared with hypertensive [i.e. spontaneously hypertensive (SH), fawn-hooded-hypertensive (FHH), and SH-stroke-prone (SHSP)] strains and obese [i.e. SH-heart failure-prone (SHHF) and JCR:LA-cp, atherosclerosis-prone (JCR)] strains. SH were slower to acclimate to the FWBP chambers. At 0-h post-air-exposure, SHSP and SHHF exhibited hyperpnea, indicative of cardiopulmonary insufficiency. At 0-h-post-O₃, all but one strain showed significant concentration-dependent decreases in minute volume [MV = tidal volume (TV) × breathing frequency]. Comparing air with 1.0 ppm responses, MV declined 20–27% in healthy, 21–42% in hypertensive, and 33% in JCR rats, but was unchanged in SHHF rats. Penh increased significantly in all strains, with disproportionate increases in “responder” WKY and FHH strains. By 20 h, most changes had resolved, although Penh remained elevated in WKY, SH, and SHSP. Based on the effective dose estimates (O₃ ppm × h × MV), the most CV-compromised (SHSP and SHHF) strains received significantly greater O₃ lung deposition (25% and 40%, respectively). Data support epidemiologic associations that individuals with cardiopulmonary insufficiency are at greater risk for urban pollutant exposure due, in part, to enhanced lung deposition and exacerbation of hypoxia and pathophysiologic processes of heart failure.

• Cardiovascular disease models
• ozone
• rat
• ventilatory parameters
• whole body plethysmography

Acknowledgements

We are grateful to Drs. Barbara Buckley and Stephen Gavett (US EPA) for their critical review of this manuscript.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency and approved for publication. Approval does neither signify that the contents necessarily reflect the views and the policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.