[Lead and blood pressure]. / Piombo e pressione arteriosa.

Evidence, even if not univocal, of increase of systolic and diastolic blood pressure for Pb doses lower than 30 microg/dl stimulated studies in the last years and opened a discussion on a possible relapse in morbility and mortality, since hypertension is an important factor of cardiovascular risk. In this study, it was possible to investigate the relationship between lead and blood pressure of 303 subjects occupationally exposed to this metal with blood-Pb between 10 and 80 microg/dl and 206 subjects belonging to the general population with blood-Pb between 0.5 and 9 microg/dl. In both groups it resulted a positive and statistically significant correlation between blood-Pb values and systolic and diastolic blood pressure values, in detail in hypertensive subjects, belonging to the not-occupationally exposed group, this effect is proportionally higher. The effect of lead on blood pressure appears therefore proved, as confirmed by previous literature, but taking into consideration three specific information. It presents itself in a large range of doses, it is quantitatively very modest, it appears more evident at low doses, thus we could hypothesize different mechanisms for different doses.

[Inorganic lead stimulates endothelin secretion in the MDCK cell line]. / Il piombo inorganico stimola la secrezione di endoteline nella linea cellulare MDCK.

BACKGROUND: Lead (Pb) is an environmental toxin whose acute intoxication causes haematological, gastrointestinal and neurological dysfunctions. Moreover it is well-established that prolonged exposure to low levels of inorganic Pb compounds is closely related to hypertension in experimental animals and occupationally exposed humans. Previous reports have suggested that endothelins (ETs), a family of peptides with potent vasoconstrictive properties, might be involved in the pathogenesis of lead-induced hypertension. In vivo studies demonstrated that rats chronically exposed to Pb low levels exhibited blood pressure elevation coupled with an increase of ET-3 concentration in plasma and urine in comparison with control animals. OBJECTIVE: Since kidney is one of the target organs of lead injury, as well as the site of production/action of ETs, we investigated the effects of an inorganic Pb compound (Pb chloride) on the synthesis and secretion of these peptides, using, as in in vitro model, a renal-derived cell line (MDCK). METHODS: The ETs assays in culture media of sub-confluent cell cultures exposed to different concentration of PbCl2 were performed by Enzyme linked Immunoassay (EIA), using two experimental procedures: a) cultures were exposed to 1100 and 200 microM PbCl2 for 30 min, next cells received Pb-free culture medium up to 24 h (pulse/chase experiment); b) cultures were fed continuously up to 24 h with treatment media containing the same PbCl2 concentrations (pulse experiment). Concomitantly, the Pb influence on cell viability was evaluated by different cytotoxicity assays (LDH release, DAPI staining and cell density assays). The mRNA expression of ET-1 was evaluated in pulse experiments by RT-PCR analysis before and after cell exposure to PbCl2. The Pb2+ cellular content of parallel MDCK cell cultures was assessed by AAS analysis. RESULTS: In our experimental conditions, the administration of PbCl2 to sub-confluent MDCK cell cultures did not significantly affect cell viability. Either in pulse or in pulselchase experiments, the ETs content, evaluated in culture media of cells exposed to 100 microM PbCl2, significantly increased. On the contrary, cell treatment with 1 or 200 microM PbCl2 did not modify the ETs secretion. Because the amounts of ETs released in culture media were similar in both kinds of experiment, our results suggest that the metal induces the ETs secretion already after 30 min of cell exposure to the toxicant. Moreover, the ET-3 EIA specific assay did not reveal any immunoreactivity, excluding the involvement of this isoform in the Pb-induced secretion of ETs. Additionally, our results seem to exclude any Pb-induced up-regulation of ET-1 transcripts. The Pb2+ quantification in cell extracts demonstrated that the uptake of the metal is dose- and time-dependent and, in pulse experiments, it was maximum after six hours from the beginning of treatments, then the intracellular Pb2+ content decreased. This last phenomenon suggests the involvement of an ATP-dependent transporter in the mechanism of Pb cell excretion. Moreover, the ETs cell release in culture media of MDCK cells appears to depend on the intracellular content of Pb ions reached within 30 min of treatment. CONCLUSION: Our results indicate that there is a range of PbCl2 doses (100 microM) at which MDCK cells enhance their ETs secretion. Lower doses (1 microM) of Pb salt seem to be ineffective to stimulate ETs release, while, doses equivalent to 200 microM seem to inhibit this phenomenon.

[Lead and cardiopathy]. / Piombo e cardiopatie.

BACKGROUND: The studies dealing with the relationship between cardiovascular disease and exposure to environmental and occupational chemical risks are out-dated and insufficient. However, this is not true of studies on lead. OBJECTIVES: This paper aims to investigate in particular the etiopathogenesis of the relationship between lead exposure and hypertension. METHODS: The studies published in the last decade concerning both the general population and occupationally exposed subjects were reviewed. RESULTS AND CONCLUSION: The effects due to high levels of exposure to lead are well known and have been studied for over a century. Knowledge on the chronic effects deriving from low and long-term exposure is still very controversial but is currently the most interesting topic; in particular lead hypertension is the topic of an increasing number of studies. Chronic exposure to low levels of lead can cause hypertension via several mechanisms. The most important are: oxidative stress associated with functional NO deficiency, elevation of sympathetic activity coupled with depressed vascular and increased renal beta receptor densities, activation of the renin-angiotensin-aldosterone system, rise in endothelin production, reduction in vasodilatatory prostaglandins and elevation of vasoconstrictive prostaglandins.