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Estimation of Aluminum, Arsenic, Lead and Nickel Status in the Samples of Different Cigarettes and their Effect on Human Health of Irish Smoker Hypertensive Consumers

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Abstract

Background: Cigarette smoking interferes with the metal homeostasis of the human body, which plays a crucial role for maintaining health. A significant flux of heavy metals, among other toxins, reaches the lungs through smoking. In the present study, the relationship between toxic element (TE) exposure via cigarette smoking and hypertension incidence in population living in Dublin, Ireland is investigated. Methods: The toxic elements arsenic (As), aluminum (Al), nickel (Ni), and lead (Pb) were determined in biological (scalp hair and, blood) samples of patients diagnosed with hypertension who are smokers living in Dublin, Ireland. These results were compared with age- and sex-matched healthy, nonsmoker controls. The different brands of cigarettes (filler tobacco, filter, and ash) consumed by the studied population were also analyzed for As, Al, Ni, and Pb. The concentrations of TEs in biological samples and different components of the cigarettes were measured by inductively coupled plasma atomic emission spectrophotometer after microwave-assisted acid digestion. The validity and accuracy of the methodology were checked using certified reference materials. Results: The recovery of all the studied elements was found to be in the range of 97.8% - 99.6% in certified reference materials. The filler tobacco of different branded cigarettes contains As, Al, Ni, and Pb concentrations in the ranges of 0.432 - 0.727 μg, 360 - 496 μg, 0.715 - 1.52 μg, and 0.378 - 1.16 μg/cigarette, respectively. The results of this study showed that the mean values of Al, As, Ni, and Pb were significantly higher in scalp hair and blood samples of hypertensive patients in relation to healthy controls, while the difference was significant in the case of smoker patients (p < 0.001). The levels of TEs were 2 - 3-fold higher in scalp hair and blood samples of non-hypertensive smoker subjects as compared to nonsmoker controls. Conclusions: The high exposure of toxic metals as a result of cigarette smoking may be synergistic with risk factors associated with hypertension.

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Article
Trace metal levels in eleven different spice and herbal plant species from western Anatolia, Turkey were determined by atomic absorption spectrometry. The contents of trace metals in the herbal plant samples were found in the ranges: 3.8–35.4 μg g−1 for copper, 0.2–2.7 μg g−1 for cadmium, 0.1–2.8 μg g−1 for lead, 1.4–11.3 μg g−1 for nickel, 0.1–9.7 μg g−1 for chromium, 30.0–945.3 μg g−1 for iron, 7.9–152.5 μg g−1 for manganese and 5.2–83.7 μg g−1 for zinc. Results obtained are in agreement with data reported in the literature.
1.1.β-Alanyl-l-histidinato zinc (AHZ), in which zinc is chelated to β-alanyl-l-histidine, is a new zinc compound. β-Alanyl-l-histidine can uniquely chelated zinc ion in various essential trace metals. More recently, it has been demonstrated that this compound has more intensive effect than zinc sulfate on bone metabolism, suggesting a role as pharmacological tool in osteoporosis. This review describes mainly the action of AHZ on bone resorption as summarized in the following.2.2. The prolonged oral administration of AHZ (10–100 mg/kg/day) can completely prevent bone loss in the femur of ovariectomized rats, indicating the preventive effect of AHZ on bone resorption in vivo.3.3. The decrease in bone calcium content induced by various bone resorbing factors was completely inhibited by the presence of AHZ (10−6-10−4 M) in bone tissue culture system in vitro.4.4. Many bone resorbing agents can stimulate the formation (differentiation) of osteoclasts from marrow cells. AHZ (10−6-10−4 M) clearly inhibited osteoclast-like cell formation in mouse marrow culture in vitro.5.5. AHZ may act on the process of parathyroid hormone-induced protein kinase C activation which is involved in Ca2+-signaling in osteoclastic cells.
Article
The levels of trace metals of canned fish samples collected from markets in Turkey were determined by flame and graphite furnace atomic absorption spectrometry after microwave digestion. The accuracy of the method was corrected by standard reference material (NRCC-DORM-2 Dogfish Muscle). The contents of investigated trace metals in canned fish samples were found to be in the range 1.10–2.50 μg/g for copper, 7.57–34.4 μg/g for zinc, 0.90–2.50 μg/g for manganese, 10.2–30.3 μg/g for iron, 0.96–3.64 μg/g for selenium, 0.45–1.50 μg/g for aluminium, 0.97–1.70 μg/g for chromium, 0.42–0.85 μg/g for nickel, 0.09–0.40 μg/g for lead and 0.06–0.25 μg/g for cadmium. The results were compared with the literature values.
Article
It was extensively investigated that a significant flux of toxic metals, along with other toxins, reaches the lungs through smoking. In present study toxic metals (TMs) (Al, Cd, Ni and Pb) were determined in different components of Pakistani local branded and imported cigarettes, including filler tobacco (FT), filter (before and after normal smoking by a single volunteer) and ash by electrothermal atomic absorption spectrometer (ETAAS). Microwave-assisted digestion method was employed. The validity and accuracy of methodology were checked by using certified sample of Virginia tobacco leaves (ICHTJ-cta-VTL-2). The percentages (%) of TMs in different components of cigarette were calculated with respect to their total contents in FT of all branded cigarettes before smoking, while smoke concentration has been calculated by subtracting the filter and ash contents from the filler tobacco content of each branded cigarette. The highest percentage (%) of Al was observed in ash of all cigarettes, with range 97.3-99.0%, while in the case of Cd, a reverse behaviour was observed, as a range of 15.0-31.3% of total contents were left in the ash of all branded cigarettes understudy.
Article
The aim of the study was to evaluate zinc levels in three biological compartments (serum, erythrocytes and hair) in patients with rheumatoid arthritis (RA) as compared to healthy individuals. Zinc levels in serum, erythrocytes and hair (in 74 patients with RA and 30 healthy individuals) were assessed by atomic absorption spectroscopy. The mean hair zinc content was significantly lower in RA patients as compared to healthy individuals (p < 0.001). Moreover, a positive correlation was observed in the RA patient group between the erythrocyte zinc levels and the prednisone dose (r s = 0.48, p < 0.05), and a negative correlation was found in this population between the serum zinc levels and disease duration (r s = −0.42, p < 0.0006). In conclusion, it seems that hair may be a useful complementary study material for evaluating “zinc status” in rheumatoid arthritis patients.
Article
The acute effects of low concentrations of aluminium (10(-12)-10(-3)m) in neural cell culture were investigated over 1-48 hr. Mitochondrial and lysosomal activities were used as measures of metabolic change after aluminium administration to C1300 mouse-derived neuroblastoma cells (C1300 N2A) and primary mixed cultures of rat embryonic mid-brain. Very rapid increases in mitochondrial and lysosomal activity occurred over periods as short as 3 hr. The aluminium-induced metabolic changes in C1300 N2A cells were compared with those produced by iron. The similar time course of metabolic events observed with iron is suggestive of a similar neurotoxicological mechanism. Experiments examining the effect of preincubation with the free radical scavenger, alpha-tocopherol (200 mum), on the aluminium and iron induced changes in primary rat mid-brain cultures, showed an inhibition of these short-term metabolic events.
Article
Metals are an important and emerging class of carcinogens. At least three metals, specifically nickel, chromium, and arsenic, are confirmed human carcinogens, and several more are suspected to have carcinogenic potential in man. Considering that the list of known human carcinogens of any type is very small, it becomes clear that metals make up a substantial portion of the list. Furthermore, many metals are very potent carcinogens in laboratory animals. Despite this, relatively little attention has been given to the topic of metal carcinogenesis. The reasons for this relative lack of attention are not clear but perhaps are fostered by a perception that, because metals are the simplest of molecules, their mechanism of action must also be simple. This could not be farther from the truth and, although no clear mechanisms have emerged in the area of metal carcinogenesis, it has become apparent that they are anything but simple. Metal carcinogens possess several unique characteristics including a remarkable target site specificity. Detection of the mechanism, or mechanisms, of metal carcinogenesis has, however, proven elusive, in part because of a wide diversity of metallic carcinogenic agents and the intricate nature of metal interactions in biologic systems. The following review explores this broad topic, with special emphasis on toxicological principles including dose-response relationships and potential mechanisms, using cadmium as an example.
Article
While the harmful health effects of carbon monoxide, nicotine, tar, irritants and other noxious gases that are present in tobacco smoke are well known, those due to heavy metals and other toxic mineral elements in tobacco smoke are not sufficiently emphasized. Tobacco smoking influences the concentrations of several elements in some organs. This review summarizes the known effects of some trace elements and other biochemically important elements (Al, As, Cd, Cr, Cu, Pb, Mn, Hg, Ni, Po-210, Se, and Zn) which are linked with smoking. Cigarette smoking may be a substantial source of intake of these hazardous elements not only to the smoker but also, through passive smoking, to nonsmokers. The adverse health effects of these toxic elements on the fetus through maternal smoking, and on infants through parental smoking, are of special concern.
Article
Fluoride is known to have biological effects on bone cells as well as physicochemical effects on bone crystals. This review concentrates on the latter. Fluoride increases the stability of the apatite lattice and decreases the solubility of the apatite crystals. In bone mineral, this ion has been shown to affect bone crystal structure by increasing crystallinity and reducing specific surface area. These changes in turn lead to changes in the chemistry of bone mineral. Bone mineral deposition is delayed by fluoride. This ion does not diffuse into bone already formed, but is incorporated during mineralization. Subsequently fluoride tends to accumulate in the most highly mineralized bone. Bone treated with fluoride has been shown to be more resistant to acid dissolution than normal bone, which would explain the reduced rate of resorption of fluoridated bone. The distribution of fluoride in bone is not uniform, but its net effect is to increase bone mineral density probably by an increased packing of bone crystals. Finally, there is a debate as to whether fluoride produces a bone of different quality. Whether these changes in the quality of bone will prove to be helpful or harmful remain to be determined.
Article
The serum copper levels of 46 elderly patients with fractures of the femoral neck were assayed and found to be significantly lower than those of a group of controls matched for age and sex. These findings are consistent with nutritional copper deficiency which may contribute to the development of fractures by reducing bone strength.
Article
This review is intended to focus attention on the importance of essential metallo-element metabolism, particularly copper metabolism, as an important component of normal bone metabolism in maintenance and repair. Literature published since Rademacher's early (1) astute observation that copper supplementation increases the rate of bone healing documents and explains key roles of copper-dependent processes required for maintenance and repair of this tissue. State of the art approaches to treatment of bone diseases including lengthening of bone and repair of fractures, can be improved by paying closer attention to the roles of copper and other essential metallo-elements required for optimal treatment.
Article
Aluminium salts do not themselves stimulate peroxidation of ox-brain phospholipid liposomes, but they greatly accelerate the peroxidation induced by iron(II) salts at acidic pH values. This effect of Al(III) is not seen at pH 7.4, perhaps because Al(III) salts form insoluble complexes at this pH in aqueous solution. Peroxidation of liposomes in the presence of Al(III) and Fe(II) salts is inhibited by the chelating agent desferrioxamine, and by EDTA and diethylenetriaminepentaacetic acid at concentrations greater than those of Fe(II) salt. Aluminium salts slightly stimulate the peroxidation of peroxide-depleted linolenic acid micelles, but they do not accelerate the peroxidation induced by addition of iron(II) salts to the micelles at acidic pH. Aluminium salts accelerate the peroxidation observed when human erythrocytes are treated with hydrogen peroxide at pH 7.4. Desferrioxamine decreases the peroxidation. We suggest that Al(III) ions produce an alteration in membrane structure that facilitates lipid peroxidation, and that the increased formation of fluorescent age pigments in the nervous system of patients exposed to toxic amounts of Al(III) may be related to this phenomenon. The ability of desferal to bind both iron (III) and aluminium(III) salts and to inhibit lipid peroxidation makes it an especially useful chelating agent in the treatment of 'aluminium overload'.
Article
Osteoporosis, a major health problem in all Western countries, is a condition in which many dietary factors have been implicated. To determine the influence of diet on bone mass in the proximal femur, the intake of 14 nutrients was measured in 159 Caucasian women, aged 23-75 years and bone mineral density (BMD) quantitated in the hip by dual photon absorptiometry. BMD was also measured in the spine and bone mineral content (BMC) in the forearm by single photon absorptiometry. No significant correlation was found between current calcium intake and bone mass at any site. Iron was a positive predictor of BMD in the femoral neck and alcohol intake a positive predictor of BMD in the trochanteric region of the proximal femur in premenopausal women by multiple regression analysis. Iron, zinc and magnesium intake were positively correlated with forearm BMC in premenopausal women. Iron and magnesium were significant predictors of forearm BMC in premenopausal and postmenopausal women respectively by multiple regression analysis. These results suggest that bone mass is influenced by dietary factors other than calcium.
Article
Plasma selenium levels, erythrocyte selenium levels and activity of the selenoenzyme glutathione peroxidase in erythrocytes were determined in patients with rheumatoid arthritis (RA) and acute inflammatory arthritis. Results were compared with those from age and sex matched controls. These variables were not statistically different from controls in patients with inflammatory arthritis and in patients with RA not treated with corticosteroids. No correlation was found in RA between plasma selenium biological variables of inflammation and most clinical indices of disease severity. Therefore, acute or chronic inflammation was not the main factor that accounted for low plasma selenium levels in RA. Corticosteroid treatment, particularly at high doses (20-60 mg prednisolone/day), was significantly related to the depressed plasma selenium levels of some patients with RA. The mechanisms underlying this modification remain poorly understood.
Article
By the use of the nuclear microprobe technique, the concentrations of zinc in isolated erythrocytes, platelets, and granulocytes were measured in patients with rheumatoid arthritis, other inflammatory arthritides, and scleroderma. Markedly reduced cellular zinc values were found compared to those measured in healthy subjects. No relation was found to inflammatory activity or disease duration. Plasma zinc was reduced in the majority of the patients and was negatively correlated to the inflammatory activity estimated by ESR and serum orosomucoid. No relation was found between total zinc values in plasma or cells or disease duration. Corticosteroid therapy was instituted in a number of the patients with inflammatory arthritides and induced a significant elevation of total zinc in all cell types, although normalization was not achieved. Plasma zinc values remained unchanged during the treatment.
Article
Having observed previously that the reduction of levels of biological markers of nutrition in postmenopausal osteoporosis may be related to zinc deficiency, we measured plasma and urinary zinc concentrations in 30 women with postmenopausal osteoporosis and in 30 healthy postmenopausal women who served as controls. Plasma zinc levels did not differ between groups, but urinary zinc excretion was significantly higher in the women with postmenopausal osteoporosis (p = 0.002). The relation between total body bone mineral content corrected for body weight (TBBMC/W) and markers of nutrition was significant (multiple regression analysis: p < 0.0001) in the women with postmenopausal osteoporosis but not in the healthy postmenopausal controls. Likewise, the relation between TBBMC/W and plasma and urinary zinc levels also was significant in the women with postmenopausal osteoporosis but not in the controls (multiple regression analysis: p = 0.0022). Neither group showed any correlation between plasma or urinary zinc concentrations and levels of biological markers of nutrition. Urinary zinc concentration correlated significantly with serum tartrate-resistant acid phosphatase level (simple linear regression analysis: r = 0.583, p < 0.001) in the women with postmenopausal osteoporosis but not in controls. TBBMC correlated with urinary zinc concentration significantly in the women with postmenopausal osteoporosis (simple linear regression: r = 0.567, p = 0.0015), but the correlation was nonsignificant in healthy postmenopausal controls. These findings indicate that the elevation of urinary zinc elimination in osteoporosis is dependent on bone resorption.
Article
A review is presented of the role of Se in rheumatoid arthritis. Areas covered include Se in inflammation and immunity, Se-dependent glutathione peroxidase, effects of Se supplementation and Se interaction with antirheumatic drugs. Some of the results that have been obtained from studies on patients with rheumatoid arthritis are presented. (57 references).
Article
The role of reactive oxygen species, with the subsequent oxidative deterioration of biological macromolecules in the toxicities associated with transition metal ions, is reviewed. Recent studies have shown that metals, including iron, copper, chromium, and vanadium undergo redox cycling, while cadmium, mercury, and nickel, as well as lead, deplete glutathione and protein-bound sulfhydryl groups, resulting in the production of reactive oxygen species as superoxide ion, hydrogen peroxide, and hydroxyl radical. As a consequence, enhanced lipid peroxidation. DNA damage, and altered calcium and sulfhydryl homeostasis occur. Fenton-like reactions may be commonly associated with most membranous fractions including mitochondria, microsomes, and peroxisomes. Phagocytic cells may be another important source of reactive oxygen species in response to metal ions. Furthermore, various studies have suggested that the ability to generate reactive oxygen species by redox cycling quinones and related compounds may require metal ions. Recent studies have suggested that metal ions may enhance the production of tumor necrosis factor alpha (TNF alpha) and activate protein kinase C, as well as induce the production of stress proteins. Thus, some mechanisms associated with the toxicities of metal ions are very similar to the effects produced by many organic xenobiotics. Specific differences in the toxicities of metal ions may be related to differences in solubilities, absorbability, transport, chemical reactivity, and the complexes that are formed within the body. This review summarizes current studies that have been conducted with transition metal ions as well as lead, regarding the production of reactive oxygen species and oxidative tissue damage.
Article
We studied the status of copper and zinc in rheumatoid arthritis (RA). The aims of the work were to ascertain whether or not RA is associated with copper and/or zinc deficiency, to establish the relationship between these trace metals and the main biohumoral and clinical indices of the disease, and to examine the effect on copper and zinc of the drugs normally used by RA patients. Metal levels were measured by atomic absorption spectroscopy in the plasma, whole blood cells and 24 hr urine of 120 RA patients; 70 patients suffering from primary osteoarthritis were used as the control group. In the plasma of RA patients copper and ceruloplasmin levels were found to be significantly increased whereas zinc levels were significantly decreased. No major variations were observed in the blood cell and 24 hr urine copper and zinc levels. Plasma copper was significantly correlated with some of the biohumoral markers of RA, but did not correlate with any of the clinical indices of the disease. Plasma zinc was significantly correlated with numerous of the biohumoral as well as clinical markers of RA. With the exception of an increased urinary excretion of copper in D-penicillamine treated RA patients, drug therapy did not influence the copper status in RA. Conversely, plasma zinc was found to be lower in RA patients taking NSAIDs and/or steroids. These results suggest the following conclusions: i) RA patients do not seem to be deficient in either copper or zinc; ii) plasma copper appears to be a poor index of RA severity; iii) plasma zinc could have some practical value in defining the overall severity of the disease.
Article
Aluminum (Al) is unquestionably neurotoxic in both experimental animals and certain human diseases. Minute quantities injected intracerebrally into rabbits will induce severe neurological symptoms and neuropathological features of neurodegeneration. Hyper-aluminemia often develops in patients with renal failure being treated with intermittent hemodialysis on a chronic basis, and in severe cases results in an encephalopathy. Uremic adults and premature infants not on dialysis treatment also can develop encephalopathy due to Al toxicity, as is the case when large amounts of alum are used as a urinary bladder irrigant. There are many other examples of Al-induced neurotoxicity; however, the question as to whether Al presents a health hazard to humans as a contributing factor to Alzheimer's disease is still the subject of debate. Several lines of evidence are presented that have formed the basis of the debate concerning the possible pathogenic role for Al in Alzheimer's disease. Important evidence for an Al-Alzheimer's causal relationship is the observation by laser microprobe mass analysis (LMMS) of the presence of Al in neurofibrillary tangles, although there are conflicting data on the extent of the Al deposition. The relatively poor sensitivity of some of the analytical instruments available for these challenging in situ microanalyses could explain the discrepant results, although LMMS and perhaps secondary ion mass spectrometry (SIMS) appear to be sufficiently sensitive. Harmonization of the techniques is an essential next step. There is new evidence that exposure to Al from drinking water might result in cognitive impairment and an increased incidence of Alzheimer's disease. However, these epidemiological studies have inherent problems that must be scrutinized to determine if an association really does exist. An understanding of a possible enhanced bioavailability of Al in this type of exposure, versus other exposures such as antacid intake or industrial exposure, needs to be considered and explored. There has been one promising clinical trial of the treatment of Alzheimer's disease patients with the Al chelator desferrioxamine (DFO). Further studies are needed, and if confirmation is forthcoming then such data could also support an Al-Alzheimer's disease link as well as suggesting that DFO offers potential as a therapeutic agent. The possibility that iron might be the offending agent needs to be considered since DFO is a very strong iron chelator. The significance of Al-induced neurofibrillary degeneration in experimental animals should be assessed especially in light of new data showing that this model exhibits abnormally phosphorylated tau protein structures in the neuronal perikarya. Thus the key questions that must be answered before it can be asserted that Al possesses causal relationship to Alzheimer's disease, are as follows and are addressed in this present discussion: (1) Are there elevations of the concentration of Al in the brains of Alzheimer's disease patients? (2) Is there a relationship between environmental exposure to Al, particularly in drinking water, and an increased risk of Alzheimer's disease? (3) Is treatment with DFO a potentially useful therapeutic approach and to what extent might beneficial effects of DFO implicate Al in the etiology of Alzheimer's disease? (4) Are there similarities between the experimental animal studies and Alzheimer's disease particularly in the development of abnormal forms of tau seen in neurofibrillary tangles? (5) Does Al promote the deposition of the A beta peptide in Alzheimer's disease? (6) Does hyperaluminemia associated with long-term hemodialysis treatment induce neurofibrillary degeneration? If the answer to each of these six questions is yes, then does this assert that Al possesses a causal relationship to Alzheimer's disease? On the other hand, must all six be met to be able to make this assertion?
Article
Salts and organic derivatives of arsenic and antimony are quite toxic. Living organisms have adapted to this toxicity by the evolution of resistance mechanisms. Both prokaryotic and eukaryotic cells develop resistance when exposed to arsenicals or antimonials. In the case of bacteria resistance is conferred by plasmid-encoded arsenical resistance (ars) operons. The genes and gene products of the ars operon of the clinically-isolated conjugative R-factor R773 have been identified and their mechanism of action elucidated. The operon encodes an ATP-driven pump that extrudes arsenite and antimonite from the cells. The lowering of their intracellular concentration results in resistance. Arsenate resistance results from the action of the plasmid-encoded arsenate reductase that reduces arsenate to arsenite, which is then pumped out of the cell.
Article
The plasma selenium (Se) levels were determined in patients with rheumatoid arthritis (RA) and healthy controls. Plasma Se levels in 60 patients were found to be significantly lower than those in 60 normal, healthy controls (p<0.001). Similar significant differences were determined in sex-matched comparisons between patients and controls (p<0.001) but there was no significant difference in plasma Se levels in sex-matched comparisons in both groups (p>0.05). Our results suggest that Se is an important factor in RA.
Article
To study zinc absorption in patients with active rheumatoid arthritis (RA). We studied zinc tolerance tests and 24 hour urinary zinc excretion before and after ingestion of 50 mg elemental zinc in 8 healthy volunteers (Group 1) and 13 patients with low RA activity (Group 2) and 16 patients with high RA activity (Group 3). In Group 1, plasma zinc rose from 111 +/- 7 micrograms/dl to a peak of 200 +/- 24 micrograms/dl (mean +/- SEM) in 2 h. In Groups 2 and 3, plasma zinc before zinc ingestion was significantly lower than that of the control group (p < 0.00001 for both groups) and showed no significant increase in plasma after ingestion. Twenty-four hour urinary zinc excretions before and after zinc ingestion were significantly lower (p < 0.01, p < 0.0001 for Group 2; p < 0.05, p < 0.01 for Group 3, respectively) than those in the control group. These results are compatible with zinc malabsorption and consequent zinc deficiency in patients with RA. Whether zinc deficiency contributes to perpetuation of disease activity by compromising cellular immune function needs further investigation.
Article
In the rat, intracerebroventricular (i.c.v.) injection of cadmium, a pollutant with long biological half-life, causes a sustained increase in blood pressure at doses that are ineffective by peripheral route. Since cadmium inhibits calcium-calmodulin constitutive nitric oxide (NO) synthase in cytosolic preparations of rat brain, this mechanism may be responsible for the acute pressor action of this heavy metal. To test this possibility, we evaluated the effect of i.c.v. injection of 88 nmol cadmium in normotensive unanaesthetized Wistar rats, which were i.c.v. pre-treated with: (1) saline (control), (2) L-arginine (L-Arg), to increase the availability of substrate for NO biosynthesis, (3) D-arginine (D-Arg), (4) 3-[4-morpholinyl]-sydnonimine-hydrochloride (SIN-1), an NO donor, or (5) CaCl2, a cofactor of brain calcium-calmodulin-dependent cNOSI. In additional experiments, the levels of L-citrulline (the stable equimolar product derived from enzymatic cleavage of L-Arg by NO synthase) were determined in the brain of vehicle- or cadmium-treated rats. The pressor response to cadmium reached its nadir at 5 min (43±4 mmHg) and lasted over 20 min in controls. L-Citrulline/protein content was reduced from 35 up to 50% in the cerebral cortex, pons, hippocampus, striatus, hypothalamus (P<0.01) of cadmium-treated rats compared with controls. Central injection of NG nitro-L-arginine-methylester (L-NAME) also reduced the levels of L-citrulline in the brain. Both the magnitude and duration of the response were attenuated by 1.21 and 2.42 μmol SIN-1 (32±3 and 15±4 mmHg, P<0.05), or 1 μmol CaCl2 (6±4 mmHg, P<0.05). Selectivity of action exerted by SIN-1 was confirmed by the use of another NO donor, S-nitroso-N-acetyl-penicillamine (SNAP). Both L-Arg and D-Arg caused a mild but significant attenuation in the main phase of the pressor response evoked by cadmium. However, only L-Arg reduced the magnitude of the delayed, pressor response. Despite their similarity in ability to attenuate the cadmium-induced pressure effect, L-Arg and its isomer exerted differential biochemical changes in brain L-citrulline, as L-Arg normalized cadmium-induced reduction in L-citrulline levels, whereas i.c.v. D-Arg did not. We conclude that the pressor effect of i.c.v. cadmium is due, at least in part, to reduced NO formation, consequent to inhibition of brain NO synthase. Accumulation of cadmium in the central nervous system could interfere with central mechanisms (including NO synthase) implicated in the regulation of cardiovascular function. British Journal of Pharmacology (1998) 123, 129–135; doi:10.1038/sj.bjp.0701573