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Insight into molecular mechanisms of ultrafine carbon particle induced cardiovascular impairments in spontaneously hypertensive rats.
Citation:
Upadhyay, S., V. Harder, R. THOMAS, M. Behnke-Semmler, S. Takenaka, E. Karg, P. Reitmeir, M. Bader, A. Stampfl, U. P. KODAVANTI, T. Stoeger, AND H. Schulz. Insight into molecular mechanisms of ultrafine carbon particle induced cardiovascular impairments in spontaneously hypertensive rats. Presented at American Thoracic Society 2008 International Conference, Toronto, ON, CANADA, May 16 - 21, 2008.
Impact/Purpose:
This study was designed to address the mechanisms of ultrafine carbon particle induced cartiopulmonary injury. the data demonstrates that ultrafine carbon particles induce delayed pulmonary response and activation of coagulation and endothelin system, without appraent inflammation following acute exposure in pypertensive rats.
Description:
Rationale: Exposure to ambient particulate matter is a risk factor for cardiopulmonary disease as identified in several epidemiological studies. Radio telemetric analysis detected increased heart rate and blood pressure in Spontaneously Hypertensive Rats (SHR) following inhalation of ultrafine carbon particles (UfCP) with a lag of 1-3 days. Therefore we aimed to elucidate the molecular mechanism associated with these observations. Methods: Biomarkers of blood pressure, oxidative stress, blood coagulation, endothelial function and inflammation were assessed from bronchoalveolar lavage fluid (BAL), blood, lung and heart tissues of UfCP exposed adult (6 months) and geriatric SHRs (12 months) compared to their control. Results: BAL cell count and differential as well as other inflammatory markers were not affected. Significant induction of hemoxygenase-1, endothelin receptor A and B; endothelin 1 (End-1), tissue factor, and plasminogen activator inhibitor 1 were observed in lungs of exposed adult and geriatric rats on the 1st and 3rd recovery days. End-1 is the only marker differentially regulated in the heart of exposed SHRs. In addition, alteration of blood pressure is supported by significant increases of renin concentration in plasma of adult SHRs during the first three days of recovery. Conclusions: These data implies that ufCP exposure triggers direct particulate matter mediated effects in pulmonary tissues that cause cardiovascular impairment and affects the blood coagulation balance. Pulmonary oxidative stress, activation of the endothelin and the renin-angiotensin system associated with induction of blood coagulation and inhibition of fibrinolysis rather than an inflammatory reaction seems to be involved in the complex response.