The negative inotropic effects of gaseous sulfur dioxide and its derivatives in the isolated perfused rat heart

Epidemiological investigations have revealed that sulfur dioxide (SO 2 ) exposure is linked to cardiovascular diseases. The present study was designed to investigate the negative inotropic effects of gaseous SO 2 and its derivatives in the isolated perfused rat heart and the possible mechanisms involved in their effects. The results showed that both SO 2 and SO 2 derivatives elicited a negative inotropic effect in a dose‐dependent manner, and SO 2 produced a higher negative effect than SO 2 derivatives. The mechanism of SO 2 ‐induced negative inotropic effects at low concentrations was different from that at high concentrations. At low concentrations, the mechanism of SO 2 ‐induced negative inotropic effects might occur through promoting the activities of protein kinase C (PKC), cycloxygenase, and cGMP, while the mechanism of SO 2 derivatives‐induced effects might be related to the opening of ATP‐sensitive K + (K ATP ) channel and the inhibition of Ca 2+ influx via L‐type calcium‐channel. At high concentrations, the mechanisms of SO 2 and SO 2 derivatives‐induced negative inotropic effects were similar, which might be related to the K ATP channel and L‐type calcium‐channel as well as the possible alterations in PKC, cycloxygenase, and cGMP. Further work is needed to determine the relative contribution of each pathway in SO 2 ‐mediated inotropic effect. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.