Efeitos cardiovasculares da exposição crônica a cloreto de mercúrio em ratos

Abstract

The evaluation of environmental exposure to small quantities of mercury showed that the metal affects the cardiovascular system. The chronic exposition produces hypertension and correlates with cardiovascular events and promotes oxidative stress. Our objective was to study the effects of 20 nM HgCl2 exposure during 30 days on hemodynamic parameters and cardiac contractility. Wistar rats were divided at random in 2 groups. The control group received intramuscular injections (IM) of saline during 30 days and the treated group received, in the first day, one IM injection containing HgCl2 sufficient to produce a plasma concentration of 20 nM HgCl2. Until the end of the treatment period rats received a supplement dose to maintain the desired plasma concentration. After 30 days rats were anesthetized, received heparin and the right carotid artery and jugular vein were cannulate, for measurements of systolic, diastolic and mean arterial pressure, left and right systolic and diastolic ventricular pressure and their time derivatives. In isolated perfused rats according to the Langendorff technique contractile characteristics were investigated. A latex balloon, connected to a pressure transducer was used to measure isovolumetric left ventricular systolic and diastolic pressures. The following protocols were performed: progressive increments of diastolic pressure and the answer to β-adrenergic stimulation. Throughout the experiment the coronary mean perfusion pressure was measured (CPP). Cardiac contractility was also evaluated in left ventricle papillary muscles: inotropism, temporal parameters, sarcoplasmic reticulum activity, sarcolemmal calcium permeability and the role of contractile proteins. The myocardial activities of Na+ -K+ -ATPase (NKA) and myosin Ca2+ ATPase were also measured. Statistical analyses: two-way ANOVA and the Student t- test. p< 0,05 was considered significant. Hemodynamic parameters showed one single alteration, the increase of the left ventricular end diastolic pressure (LVEDP) in the Mercury group when compared to control. However, in isolated hearts it was observed in the HgCl2 group reduction of developed pressure and time derivatives in control conditions and in all diastolic pressures. The hearts from the Mercury group also showed a reduction of the βadrenergic response. Moreover, the HgCl2 chronic treatment was not capable to alter the contractile parameters in left ventricle papillary muscles, but increased the myosin Ca2+ ATPase and the NKA specific activity. Possibly the LVEDP increase in vivo and the negative inotropic effect observed in isolated hearts are linked to the NKA inhibition that causes an increase of intracellular calcium inducing a defective relaxation by the myocardium calcium overload. Considering that the hemodynamic parameters are preserved in vivo we could speculate that neuro-humoral factors might be playing a role to maintain the cardiac inotropic state and the arterial pressure. The increased activity of the myosin Ca2+ ATPase might also be a compensatory mechanism of the cardiac muscle. We suggest that the reduction of the β-adrenergic response is a consequence of a desensitization process caused by an increased sympathetic tone as a compensatory mechanism during HgCl2 exposure. We might conclude that the chronic exposure to a small concentration of HgCl2 produces a negative inotropic effect in isolated hearts, a relaxation deficit in vivo and an increase of myosin ATPase activity and NKA inhibtion.