Electromechanical effects of urea on the isolated rat heart

1. Langendorff-perfused isolated hearts and left ventricle papillary muscles from 3-month-old albino rats of both sexes were studied before and after a 30-min treatment with 17 mM urea added to the medium, a concentration equivalent to a plasma level of 100 mg/dl. To determine whether the effects observed after the addition of urea were produced by an increase in tonicity, the study was repeated using 17 mM sucrose. 2. Mechanical studies on the papillary muscles showed that isometric force development and its first time derivative decreased after washing out urea from the bath (F = 9.73 +/- 1.02 g/mm2 to 7.47 +/- 0.72 and dF/dt = 66.8 +/- 6.43 to 56.7 +/- 4.60 g (mm2)-1 s-1, respectively; P < 0.05). Inotropic responses to isoproterenol and increased extracellular calcium after urea treatment reached values similar to those obtained before urea treatment. Thus, the effect of isoproterenol and calcium was stronger than that obtained before urea treatment. 3. In Langendorff-perfused hearts, the spontaneous heart rate did not change after urea or sucrose treatment. Urea promoted a decrease in the left ventricle isovolumic systolic pressure (39.7 +/- 4.05 to 26.1 +/- 2.69 mmHg, P < 0.05) and a reduction of total QRS amplitude. 4. In both papillary muscles and isovolumic perfused hearts, contractile responses resulting from changes in extracellular sodium concentration were reduced after urea treatment. The increased osmolarity due to sucrose did not produce any changes in electromechanical activities. 5. Although 17 mM, which reduces isometric force and isovolumic pressure development and modifies the ECG, is well below the concentration required to modify protein conformation in vitro, the present results suggest that its action could be explained by an effect at the sarcolemmal level.