Chronic mercury exposure at different concentrations produces opposed vascular responses in rat aorta.

Mercury chloride exposure for 30 days decreases NO bioavailability and increases oxidative stress. However, the mechanisms underlying the effects of mercury on the cardiovascular system are not completely understood, and it is not known if they are dose-dependent or if some concentrations have no harmful effects. Thus, we investigated the effects of chronic exposure to doses low (half) and high (2.5-fold higher) than that needed to obtain 29 nmol/L of HgCl2 on the vascular function. Three-month-old male Wistar rats received intramuscular (i.m.) HgCl2 for 30 days and were divided in three groups: lower (Low Hg); higher (High Hg); and saline was used as the control. High Hg exposure increased the contractile response to phenylephrine (PHE) in aortic rings, but Low Hg reduced it. The hyporesponsiveness in the Low Hg rats was blunted by endothelial denudation and NOS inhibition with l-NAME (100 µmol/L). The phosphorylated-eNOS/eNOS protein ratio increased in the aortas of Low Hg rats. In the High Hg group, endothelial denudation increased the PHE-induced contractions, while l-NAME had no effects and indomethacin (10 µmol/L), losartan (10 µmol/L) and apocynin (30 µmol/L) reduced this response. In the High Hg group, protein levels of the NADPH oxidase subunit gp91phox and cyclooxygenase-2 increased. Our results support previous suggestions that High Hg increases oxidative stress that might activate an inflammatory cascade and the renin-angiotensin system. However, very low Hg concentrations below the level considered safe still reduced vascular reactivity, suggesting the need for special attention to continuous exposure as a putative cause of increased cardiovascular risk.

Chronic mercury exposure impairs the sympathovagal control of the rat heart.

Mercury is known to cause harmful neural effects affecting the cardiovascular system. Here, we evaluated the chronic effects of low-dose mercury exposure on the autonomic control of the cardiovascular system. Wistar rats were treated for 30 days with HgCl2 (1st dose 4.6 µg/kg followed by 0.07 µg/kg per day, intramuscular) or saline. The femoral artery and vein were then cannulated for evaluation of autonomic control of the hemodynamic function, which was evaluated in awake rats. The following tests were performed: baroreflex sensitivity, Von Bezold-Jarisch reflex, heart rate variability (HRV) and pharmacological blockade with methylatropine and atenolol to test the autonomic tone of the heart. Exposure to HgCl2 for 30 days slightly increased the mean arterial pressure and heart rate (HR). There was a significant reduction in the baroreflex gain of animals exposed to HgCl2 . Moreover, haemodynamic responses to the activation of the Von Bezold-Jarisch reflex were also reduced. The changes in the spectral analysis of HRV suggested a shift in the sympathovagal balance toward a sympathetic predominance after mercury exposure, which was confirmed by autonomic pharmacological blockade in the HgCl2 group. This group also exhibited reduced intrinsic HR after the double block suggesting that the pacemaker activity of the sinus node was also affected. These findings suggested that the autonomic modulation of the heart was significantly altered by chronic mercury exposure, thus reinforcing that even at low concentrations such exposure might be associated with increased cardiovascular risk.

Deleterious effect of hypothermia in myocardial protection against cold ischemia: a comparative study in isolated rat hearts.

BACKGROUND: There is a growing need to improve heart preservation benefit the performance of cardiac operations, decrease morbidity, and more important, increase the donor pool. Therefore, the objective of this study was to evaluate the cardioprotective effects of Krebs-Henseleit buffer (KHB), Bretschneider-HTK (HTK), St. Thomas No. 1 (STH-1), and Celsior (CEL) solutions infused at 10°C and 20°C. METHODS: Hearts isolated from male albino Wistar rats and prepared according to Langendorff were randomly divided equally into 8 groups according to the temperature of infusion (10°C or 20°C) and cardioprotective solutions (KHB, HTK, STH-1, and CEL). After stabilization with KHB at 37°C, baseline values were collected (control) for heart rate (HR), left ventricle systolic pressure (LVSP), coronary flow (CF), maximum rate of rise of left ventricular pressure during ventricular contraction (+dP/dt) and maximum rate of fall of left ventricular pressure during left ventricular relaxation (-dP/dt). The hearts were then perfused with cardioprotective solutions for 5 minutes and kept for 2 hours in static ischemia at 20°C. Data evaluation used analysis of variance (ANOVA) in all together randomized 2-way ANOVA and Tukey's test for multiple comparisons. The level of significance chosen was P < .05. RESULTS: We observed that all 4 solutions were able to recover HR, independent of temperature. Interestingly, STH-1 solution at 20°C showed HR above baseline throughout the experiment. An evaluation of the corresponding hemodynamic values (LVSP, +dP/dt, and -dP/dt) indicated that treatment with CEL solution was superior at both temperatures compared with the other solutions, and had better performance at 20°C. When analyzing performance on CF maintenance, we observed that it was temperature dependent. However, when applying both HTK and CEL, at 10°C and 20°C respectively, indicated better protection against development of tissue edema. Multiple comparisons between treatments and hemodynamic variable outcomes showed that using CEL solution resulted in significant improvement compared with the other solutions at both temperatures. CONCLUSION: The solutions investigated were not able to fully suppress the deleterious effects of ischemia and reperfusion of the heart. However, these results allow us to conclude that temperature and the cardioprotective solution are interdependent as far as myocardial protection. Although CEL solution is the best for in myocardial protection, more studies are needed to understand the interaction between temperature and perfusion solution used. This will lead to development of better and more efficient cardioprotective methods.

Toxic effects of mercury, lead and gadolinium on vascular reactivity.

Heavy metals have been used in a wide variety of human activities that have significantly increased both professional and environmental exposure. Unfortunately, disasters have highlighted the toxic effects of metals on different organs and systems. Over the last 50 years, the adverse effects of chronic lead, mercury and gadolinium exposure have been underscored. Mercury and lead induce hypertension in humans and animals, affecting endothelial function in addition to their other effects. Increased cardiovascular risk after exposure to metals has been reported, but the underlying mechanisms, mainly for short periods of time and at low concentrations, have not been well explored. The presence of other metals such as gadolinium has raised concerns about contrast-induced nephropathy and, interestingly, despite this negative action, gadolinium has not been defined as a toxic agent. The main actions of these metals, demonstrated in animal and human studies, are an increase of free radical production and oxidative stress and stimulation of angiotensin I-converting enzyme activity, among others. Increased vascular reactivity, highlighted in the present review, resulting from these actions might be an important mechanism underlying increased cardiovascular risk. Finally, the results described in this review suggest that mercury, lead and gadolinium, even at low doses or concentrations, affect vascular reactivity. Acting via the endothelium, by continuous exposure followed by their absorption, they can increase the production of free radicals and of angiotensin II, representing a hazard for cardiovascular function. In addition, the actual reference values, considered to pose no risk, need to be reduced.

Toxic effects of mercury, lead and gadolinium on vascular reactivity

Heavy metals have been used in a wide variety of human activities that have significantly increased both professional and environmental exposure. Unfortunately, disasters have highlighted the toxic effects of metals on different organs and systems. Over the last 50 years, the adverse effects of chronic lead, mercury and gadolinium exposure have been underscored. Mercury and lead induce hypertension in humans and animals, affecting endothelial function in addition to their other effects. Increased cardiovascular risk after exposure to metals has been reported, but the underlying mechanisms, mainly for short periods of time and at low concentrations, have not been well explored. The presence of other metals such as gadolinium has raised concerns about contrast-induced nephropathy and, interestingly, despite this negative action, gadolinium has not been defined as a toxic agent. The main actions of these metals, demonstrated in animal and human studies, are an increase of free radical production and oxidative stress and stimulation of angiotensin I-converting enzyme activity, among others. Increased vascular reactivity, highlighted in the present review, resulting from these actions might be an important mechanism underlying increased cardiovascular risk. Finally, the results described in this review suggest that mercury, lead and gadolinium, even at low doses or concentrations, affect vascular reactivity. Acting via the endothelium, by continuous exposure followed by their absorption, they can increase the production of free radicals and of angiotensin II, representing a hazard for cardiovascular function. In addition, the actual reference values, considered to pose no risk, need to be reduced.