Abstract
Tungsten exposure is associated with multiple cardiovascular diseases, but limited information exists on the mechanistic underpinnings of these relationships. The current study investigated the individual and combined effects of angiotensin II (AT-II) treatment, as a model of accelerated cardiovascular disease risk, and tungsten (W) exposure on cardiac function, to provide insights into potential mechanisms involved in tungsten-mediated cardiac injury. Mice received AT-II (0.73 mg/kg/d) or saline (Veh) for 24 days through osmotic mini-pumps. The final 2-weeks of treatment, mice were exposed 4 times (4 h each) to filtered air (FA) or 1.50 ± 0.22 mg/m(3) W particles by whole-body inhalation. Laser ablation and bulk inductively-coupled plasma mass spectrometry (ICP-MS) of lung samples indicated an accumulation of iron in AT-II treatment groups and confirmed the deposition of W and decreases in essential elements zinc, magnesium, and molybdenum in exposure groups. Echocardiographic data showed W exposure decreased cardiac output and stroke volume; however treatment with AT-II did not further exacerbate W's effects. The A'/E' ratio was significantly elevated in the AT-II + W group compared to the W + Veh group and trending significant compared to the FA + AT-II group. Blood cardiac troponin I was elevated in the W + AT-II group compared to either FA + Veh or W + Veh groups. Results suggest an interactive effect of both W and AT-II to drive cardiac injury following exposure. However, neither W exposure nor AT-II treatment resulted in pulmonary inflammation at the terminal endpoint of the study. Data illustrate pathophysiological effects of inhaled W and AT-II that contribute to cardiac injury.