Endothelium: A Target for Harmful Actions of Metals.

The use of heavy metals is closely linked to the history of mankind. They have been used as important materials in a wide variety of human activities such as manufacturing utensils and tools. Such extended use has significantly increased professional and environmental exposure to mercury, lead and cadmium. These metals are known to produce hypertension in humans and animals and, among other effects, they can also affect endothelial function. Results described here suggest that mercury, lead and cadmium affect vascular reactivity, even at low doses or concentrations. Several vascular actions are mediated by the endothelium via increasing the production of free radicals and angiotensin II by local ACE stimulation. These results provide further evidence that these toxic metals, even at low doses, are an environmental risk factor to the exposed population. These results also suggest that continuous exposure to these metals, followed by their absorption and progressive accumulation in the body, may be hazardous to cardiovascular function. Therefore, the current reference values, which are considered safe, need to be reduced.

Mercury leads to features of polycystic ovary syndrome in rats.

Mercury (Hg) is a heavy metal and Hg exposure is associated with various neural, immune, and cardiovascular abnormalities. However, few studies have evaluated Hg's toxicologic effect on reproductive and metabolic functions. In this study, we assessed whether Hg exposure results in reproductive and metabolic abnormalities. Hg was administered to adult female Wistar rats, mimicking the Hg levels found in exposed human blood, and their reproductive and metabolic function was assessed. Rats exposed to Hg displayed abnormal estrous cyclicity and ovarian follicular development, with a reduction in ovarian antral follicles and an increase in atretic and cystic ovarian follicles. Uterine atrophy with the presence of inflammatory cells was observed in Hg-exposed rats. The presence of abnormal ovarian fat accumulation, as well as increased ovarian lipid drops accumulation, was observed in Hg-exposed rats. Ovarian oxidative stress was also present in the Hg-exposed rats. High fasting glucose levels, glucose, and insulin intolerance were observed in Hg-exposed rats. Thus, these data suggest that Hg exposure led to abnormal reproductive and metabolic features similar to those found in the polycystic ovary syndrome (PCOS) rat models.

Impaired participation of potassium channels and Na+ /K+ -ATPase in vasodilatation due to reduced nitric oxide bioavailability in rats exposed to mercury.

Mercury intoxication is a public health risk factor due to its hazardous effect to several organs, including the cardiovascular system. There is evidence of endothelial dysfunction after exposure to mercury, but the effects on endothelium-dependent vasodilatation are still unknown. In the present study, we aimed to evaluate the chronic effects of high HgCl2 doses on the mechanisms of vasodilatation. Wistar rats were injected with HgCl2 (1st dose 10.86 µg/kg, and daily doses 0.014 µg/kg for 30 days i.m.), and saline was used as control. Mercury exposure reduced the acetylcholine-induced vasodilatation in aortic rings, which was restored by incubation with antioxidant tiron. Inhibition of the NO synthase, Na+ /K+ -ATPase and K+ channels indicates reduced participation of these factors. In the mercury group, there were an increased local anion superoxide and a reduced NO. The vasodilatation to exogenous NO was partially inhibited by co-incubation with TEA plus tiron, suggesting that reduced NO bioavailability is the responsible to that decreased the participation of K+ channels. Moreover, there was an increased participation of the Na+ /K+ -ATPase associated with an up-regulation of its alpha-1 subunit. In conclusion, reduced NO bioavailability plays a major role in the impaired participation of K+ channels and Na+ /K+ -ATPase in the acetylcholine-mediated relaxation, although sodium pump is up-regulated probably as a compensatory mechanism.

High salt intake does not produce additional impairment in the coronary artery relaxation of spontaneously hypertensive aged rats.

The effect of a salt-based diet on the coronary responsiveness in aged hypertensive rats (SHR) still is unclear. We investigated the effects of high salt intake on the relaxation properties of coronary arteries of aged SHRs. Male SHR (32 week-old) received drinking water (SHR) or 1% NaCl solution (SHR-Salt) for 8 weeks. Isolated coronary segments were subjected to concentration-response curves to acetylcholine (ACh) in the presence or absence of L-NAME (100 µM), enalaprilate (10 µM), losartan (10 µM), and spironolactone (100 µM). Salt intake did not increase blood pressure in old SHRs, but caused ventricular hypertrophy. The endothelium-dependent relaxation in SHRs was lower than in Wistar rats. However, salt intake did not add further impairment. Both enalaprilate and losartan reduced the vasodilator response in coronary arteries from Wistar, but did not affect SHR-salt rats. Conversely, losartan attenuated the impaired ACh relaxation observed in SHR. Spironolactone reduced the relaxation induced by ACh in coronary arteries from Wistar rats but not in SHR. The renin-angiotensin-aldosterone system participates in the impaired coronary relaxation in aged SHR, but does not partake in this deleterious effect under increased salt intake, indicating that age could differentiate the effects of high sodium intake in coronary arteries of SHR.