3). During this inotropic intervention no changes in coronary perfusion pressure were observed. In order to investigate the underlying mechanisms that could explain those mechanical effects on hearts from mercury-treated rats, NKA and myosin ATPase activities were measured. Myocardial myosin ATPase activity was increased (Ct: 257.7 ± 11.7 vs HgCl2: 301.5 ± 9,3 nmol Pi/min/mg, P < 0.05) while NKA activity was reduced (Ct: 59.8 ± 4.5 vs HgCl2: 35.3 ± 8.6 nmol Pi/min/mg, P < 0.05) in the mercury-treated group. Protein expressions of NCX, α1 and α2 subunits of NKA, SERCA, phospholamban and its

phosphorilated fraction were measured (Fig. 4 and Fig. 5) in order to evaluate calcium handling mechanisms. After 30-day SCH727965 nmr mercury treatment reduces expression of alfa-1 NKA subunit and NCX expression, but expression of alfa-2 NKA subunit did not change. Moreover, after exposure to low doses of mercury, SERCA expression and phosphorilated phospholamban were reduced while phospholamban expression was increased. These changes led to a reduction in SERCA/PLB ratio, suggesting the reduction in calcium uptake by the sarcoplasmic reticulum contributing to the calcium overload. Since no changes CHIR-99021 solubility dmso in myocardial mass were found analyzing ventricular

weight we investigated myocardial morphology by analyzing putative actions of mercury treatment on cell morphometry. No changes for morphometric results were observed for perimeter, width, length and area of myocardial cells (results not shown). In addition, no changes Bumetanide were observed in collagen fraction in left ventricle from the mercury-treated group as compared with controls (5.1 ± 0.8 vs 4.7 ± 0.6% of tissue area). To investigate if such changes could produce hemodynamic effects, we performed measurements of systolic, diastolic, mean arterial pressure and heart rate in anesthetized rats. No differences were observed between the two groups (Table 2). The measurement of ventricular pressures, LVSP

and time derivatives also did not change. However, only LVEDP increased in the 30-day mercury-treated group. The main findings presented here show that 30-day treatment with low mercury concentration produced a negative inotropic effect in perfused hearts, although myosin ATPase activity increased. This contractility reduction was explained by alterations in calcium-handling mechanisms because of both diminished protein expression of SERCA, NKA (α1 subunit) and NCX, and increased PLB expression together with a reduced response to β-adrenergic stimulation. This treatment did not change arterial or ventricular pressures, although it produced a small but significant increase of LVEDP in anesthetized rats. Mercury is known to be an environmental risk factor for cardiovascular diseases (Houston, 2007).