effects of elements in human blood pressure control

Effects of Elements in Human Blood Pressure Control

HUBERT F. LOYKE

St. Vincent Charity Hospital, Department of Medicine, Cleveland, OH 44115

Received March 1, 2001; Revised July 17, 2001; Accepted September 17, 2001

ABSTRACT

This review enumerates and discusses the elements involved in the con-trol of human blood pressure via a historical evolutionary form. The olderand most recent element literature presentations were researched usingMEDLINE and a manual review of documents cited. Independent dataextraction and cross-referencing was performed. Of the 28 known elementsthat can influence blood pressure, 15 were found to be involved in humanblood pressure regulation. The elements were divided into four groups: elec-trolyte, composed of sodium, potassium, calcium, and magnesium; metal,which included zinc, copper, and iron; toxic, made up of lead, mercury, cad-mium, barium, thallium, arsenic; miscellaneous (lithium and selenium). Evo-lutionary historical data, possible mechanisms of actions, and interactionsbetween elements that have been shown to influence blood pressure are dis-cussed. Controversy exists over the therapeutic use of elements to alter bloodpressure but is absent in the case of the toxic group where preventive controlis a proven public health matter. The significance of these 15 elements in theregulation of human blood pressure has been established and ongoing stud-ies will continue to reinforce their influence and importance.

Index Entries: Blood pressure; elements; hypertension; minerals.

INTRODUCTION

High blood pressure is the most common disease in industrializedsociety and the ubiquitous elements play an important role in the patho-physiology and control of blood pressure. Of the 28 known elements (1),only 15 can be classified as important participants in human blood pres-sure control. The major participating elements identified as having animportant role in blood pressure regulation are sodium, calcium, potas-

Biological Trace Element Research 193 Vol. 85, 2002

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sium, and magnesium. Elements that play a minor role are identified asthe five trace elements copper, zinc, selenium, lithium, and iron and the sixtoxic ones: lead, cadmium, arsenic, barium, mercury, and thallium. Thisarticle provides an overview from an early historical perspective of theevolutionary concepts to our presentday knowledge of the relationship ofelements to human blood pressure regulation.

MATERIALS AND METHODS

The initial older and most recent presentations of element literaturewere researched using independent data extraction and cross-referencing.Manual medical review and computerized MEDLINE equipment wereemployed using the following terms: elements and blood pressure, trace ele-ments and blood pressure, and hypertension and minerals. The criteria forinclusion were assembled in a historical and chronological order of the ini-tial article on the subject. Subsequent references of new information,including epidemiological studies and meta-analysis when available, werefollowed by mechanisms of action and interactions between elements andended with the most recent new data on the subject.

ELECTROLYTE GROUP

Sodium

The relationship of the electrolytes to the elements sodium, potas-sium, calcium, and magnesium (Table 1) are highly relevant to the patho-physiology of blood pressure regulation. It was suggested as early as 1904that sodium in a high-salt intake may be implicated in the development ofhigh blood pressure (2). This idea did not gain support until Kempner (3),in the 1940s, reported that subjects with severe hypertension loweredblood pressure when treated with rigid salt restriction (e.g., rice diet).Since these reports, several studies have described societies in which rou-tine higher intakes of sodium increased blood pressure (4). Conversely, itwas shown that in societies with low-sodium intake, there is little or noincrease in blood pressure with age (5). Urinary sodium and blood pres-sure findings in the standardized INTERSALT study of 52 centers (32countries) showed a significant positive association in 8 centers and a neg-ative association in 2 centers (6). The purpose of that study was to providedefinitive data of the effect of sodium on blood pressure; however, 5 yrafter publication, the debate continued. Subsequently, it was concludedthat the general relationship between blood pressure control and saltingestion has not been sufficiently documented. A recent meta-analysis byGroudal et al. (7) of 58 trials of hypertensive persons did not support ageneral recommendation to reduce sodium intake; however a small reduc-

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tion in dietary salt in older individuals will cause a fall in blood pressure(8). One effect of the mechanism of sodium restriction shows a rise inplasma norepinephrine that results in increasing the release of renal nor-epinephrine (9). In light of the relatively weak relationship betweendietary sodium and blood pressure, Messerli et al. (10) hypothesized in1997 that a strong correlation exists between salt intake and hypertensiontarget organ disease (heart, kidney, brain, and vasculature). This inde-pendent correlation between salt intake and target organ disease suggeststhat dietary sodium is a direct perpetrator of cardiovascular disease, par-ticularly in salt-sensitive patients.

Sodium’s role in salt-sensitive subjects (Table 2) is widely acceptedand there is general agreement that the mechanism of salt sensitivity isrelated to the following: (1) plasma renin levels (11); (2) alterations in cal-cium metabolism (12); (3) some aspects of sympathetic nervous systemfunction (8–13); (4) the severity of the hypertension (14). Other informationpertinent to complications of hypertension is seen in patients withsodium-sensitive essential hypertension, where blood pressure fails to fallduring the night and this nocturnal hypertension may be a marker forgreater risk (15). Information regarding an association between the differ-ent levels of sodium intake in relation to morbidity and mortality has beenlacking. However, Alderman et al. (16) presented evidence that supportsthe likelihood that lowering sodium through dietary intervention will leadto a decrease risk of stroke and myocardial infarction, presumably by areduction in blood pressure. Also, Elliot et al. (17) concluded that a strongpositive association of urinary sodium in relation to the systolic pressureof individuals concurs with cross-population findings and supports rec-

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Table 1Elements Effects on Blood Pressure

* Increased and decreased blood pressure effects.

ommendations for reduced high-salt intake for the prevention and controlof adverse blood pressure levels. Insulin resistance has been demonstratedin patients with essential hypertension, and insulin-moderated sodiumretention is believed to contribute to hypertension in these individuals(18). In the latest collaborative study (19), it was concluded that over-weight adults having a high normal blood pressure, weight loss andreduction in sodium intake, individually and in combination, were foundto be effective, especially in lowering both systolic and diastolic bloodpressure in the short term. Thus, sodium is an important element in thecontrol of human blood pressure. Despite conflicting data regarding saltand hypertension, it is clear that at least in the elderly and salt-sensitivesubjects, salt may increase blood pressure.

Potassium

The old name “potash” was given to the element potassium and aninadequate amount of dietary potassium may be associated with essentialhypertension. As early as 1902, Bunge (20) pointed out that the electrolytepotassium (Table 2) antagonizes the biological effects of sodium and Thomp-son and McQuerrie (21) in 1934 reported that potassium salts could lowerblood pressure in hypertensive subjects. The first epidemiological study (22)was performed in 1959 in two Japanese communities with similar saltintakes. In the village where the blood pressure was lower, the potassium

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Table 2Elements and Systems in Blood Pressure Control

Systems that may be involved relative to elements in the control of human blood pressure.References pertaining to the source of the information is provided in parentheses

intake was much higher. The role of potassium, however controversial, stemsfrom experimental studies in several models of hypertension (23). A contem-porary epidemiologic study demonstrated a greater prevalence of hyperten-sion among population groups ingesting diets low in potassium (24). Watsonet al. (25), studying blacks and whites living in the same geographic area,found a higher incidence of hypertension and lower potassium intake whereurinary sodium potassium ratio was 4.1 for the blacks and 2.9 for the whites.A meta-analysis of 33 randomized controlled trials (26) support the premisethat low potassium intake may be an important factor in the genesis of highblood pressure and that potassium supplementation may be especially use-ful for black patients as well as those who have difficulty lowering dietaryintake of sodium. In contrast, the Hypertension Preventive CollaborativeResearch Group (27) found little evidence of the potassium-supplementationlowering effect of blood pressure in normotensive persons. The most recentdata strongly suggest that potassium supplementation is particularly impor-tant in patients being salt sensitive ingesting more salt than other patients(28). Tobian et al. (29) demonstrated that high potassium diets confer protec-tion against brain hemorrhage in spontaneously hypertensive rats with orwithout blood pressure reduction and Khaw and Barrett-Connor (30)described an inverse relationship between potassium intake and stroke riskin a study of American white men and women and concluded that potassiumdepletion augments human stroke-associated mortality. The mechanism ofpotassium’s effect on blood pressure is not clear. Possible actions are throughnaturetic and diuretic effects, central and peripheral effects upon the nervoussystem, and alterations in the renin–angiotensin aldosterone axis (31). Potas-sium plays an important role in the control of blood pressure, especiallyregarding diet and stroke prevention.

Calcium

The mineral ion calcium has a relationship to blood pressure home-ostasis. The case for the electrolyte calcium effect on blood pressure (Table 2)was made, later than that of the other cations in 1955, when Schroeder andPerry (32) demonstrated the antihypertensive effect of chelating agents inassociation with ion-binding calcium. Subsequently, in the 1960s, clinicaland experimental reports appeared noting the relationship between hyper-parathyroidism and hypertension (33). Interest in the effect of calcium onblood pressure levels was stimulated by the observation that persons drink-ing “hard water,” having a high concentration of calcium, had a low mor-tality and low incidence of cardiovascular disease (34). A great deal ofconfusion exists over the effects of both dietary and serum calcium levels onhypertension. To help clarify this, Harlan et al. (35), in the early 1970s ana-lyzed the data collected by the National Center for Health Statistics’ Healthand Nutrition Examination Survey I (Hanes I). Among their findings, thegroup noted that calcium was the nutrient for which reduced intake wasmost consistent in people with systolic hypertension. Conversely, hypercal-



cemia has been shown to be hypertensive in acute studies as well as inchronic azotemic patients (36). Augmenting the picture, calcium’s blood-pressure-lowering effects (Table 1) have been reported in both men andwomen as well as in the elderly (37). Epidemiological studies (38) by Beli-zoon and Villar, using meta-analysis, described finding an inverse relation-ship to exist between calcium intake and gestational hypertension ineclampsia. Subsequently, Bucher et al. (39) found that supplementation dur-ing pregnancy leads to an important reduction in systolic and diastolicblood pressure in the preeclampsia patient. Comparing black and white nor-motensive men, Lyle et al. (40) concluded that calcium supplements pro-duced a modest but significant decrease in blood pressure in both races. Onepossible mechanism of calcium supplements may be the production of reninin patients with low renin activity (Table 2) and low serum-ionized calciumlevels, blood pressure is lowered (41). In the latest reports, Weinberger et al.(42) concluded that calcium supplements decreased blood pressure inpatients identified, a priori, as being salt sensitive, although not in the gen-eral population. In a longitudinal study (37) of young children, the mainfinding was that calcium intake was inversely related to systolic blood pres-sure. Furthermore Dwyer et al. (43) found that with a low intake of calciumin the diet, African-American adolescents lowered their diastolic blood pres-sure with calcium supplements. Finally, Griffith et al. (44) concluded thatcalcium derived from a natural good source may have as much as twice thebeneficial effect of calcium supplements. This element has important appli-cations to the control of blood pressure in general medicine and obstetrics.

Magnesium

Magnesium is a trace mineral acting primarily as an intracellular ion.Over the past decade, clinical, epidemiological, and experimental data sug-gest that magnesium, the fourth most abundant cation in the human body,plays an important role in blood pressure control. Interest in the element isrelatively new in the treatment of hypertension; however, a report by Black-fan and Hamilton (45) in 1925 found that an infusion of magnesium salt low-ered blood pressure (Table 1) in some patients with hypertension. Lazard(46) in the same year reported giving an obstetrical patient intervenous mag-nesium sulfate in treating eclampsia. Likewise, McCall and Sass (46) demon-strated that, in toxemia of pregnancy, treatment with magnesium sulfatedecreased blood pressure. In 1957, the effect of magnesium action accordingto Elkington (46) was that the element caused peripheral vasodilitation witha subsequent fall in blood pressure. Aside from obstetrics, parenteral mag-nesium sulfate has been used in the treatment of severe hypertension ofglomerular nephritis (47). Epidemiological studies have described an inverserelationship between dietary intake of magnesium and blood pressure (48).Magnesium levels are not necessarily indicative of total-body magnesium;consequently, the ability to determine a deficiency is problematic. Altura andAltura (49) stated that magnesium, particularly in conjunction with other

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nutrients, does contribute to blood pressure regulation. Magnesium’s effecton the vasculature is opposite to calcium (50), in that magnesium is foundprimarily intracellulary, unlike calcium, which is extracellular. In hyperten-sion, intracellular free magnesium is deficient while calcium is elevated (50).Therefore, the regulatory role of magnesium on peripheral vascular resist-ance may have an important role in calcium uptake. Resnick et al. (51) sug-gested that calcium and magnesium homeostasis may be regulated (Table 2)by the renin – aldosterone system. The lowest quintile people having thehighest intake of magnesium in drinking water had a 20% less odds ratio ofdeaths resulting from hypertension (52). When dealing with specific hyper-tensive patients, defects in magnesium metablolism are found in young peo-ple having borderline hypertension, whereas magnesium treatment lowersthe blood pressure in patients with malignant hypertension (53). These arepotent examples of the role of this element in the control of blood pressure.With regard to magnesium supplementation, Joffres et al. (54) described aninverse relationship between dietary intake of magnesium and blood pres-sure, and Zemel et al. (55) found that in magnesium-replete hypertensivesubjects, there was no effect on blood pressure probably because magnesiumhas no effect on the cellular cation metabolism in these individuals. Proposedmechanisms of magnesium’s action on blood pressure involve renal vasodi-latation, prostacyclin release (56), and acceleration of the cell membranesodium pump (57). Interestingly, angiotensin-converting enzyme inhibitorshave an important magnesium-conserving action, possibly via their effect onglomerular filtration rate (58). Ventura et al. (59) in 1997 reported thatcyclosporine use in organ transplantation has been shown to be associatedwith hypertension. The following year, Vannini et al. (60) reported that afterkidney transplants, hypomagnesemia is a common occurrence in patients oncyclosporine therapy. Subsequently, therapy with magnesium supplementswere found by Nguyen and Steiner (61) to be protective against thecyclosporine-induced hypertension. This important element also has a rolein blood pressure control in both the obstetrical and general medical fields.

METAL GROUP

Zinc

Modification of the homeostasis of trace elements might occur inessential hypertension. The first trace element studied that is a nutritionallyessential metal was zinc. In 1961, Prasad and Oberfeas (62) first suspectedthat a nutritional zinc deficiency occurred in man, but not until 1991 werehuman hypertensive kidneys found by Perry et al. (63) to contain lowerzinc concentrations than those from normotensive subjects. Zinc participa-tion in the control of human hypertension is supported by Vivoli et al. (64),who observed a lower zinc bioavailability in hypertensive patients pertain-ing to zinc-dependent enzymes. Conflicting levels of plasma, serum, or



urine zinc concentrations have been observed between hypertensive andnormotensive subjects (64). Supporting evidence regarding zinc-dependentenzymes shows an inverse correlation between diastolic blood pressureand serum alkaline phosphotase and lactic dehydrogenase. This mightexplain a lower zinc bioavailability in the hypertensive condition. Regard-ing possible mechanisms considering the renin–angiotensin system (Table2), zinc may be involved because the angiotensin-converting enzyme is azinc-containing peptide (65). Zinc is often related to copper, and in 1995,Vivoli et al. (64) concluded that an imbalance between both copper and zinc(Table 1) might be involved in human hypertension. The decrease in arte-rial blood pressure during zinc deficiency indicates that zinc metabolism isinvolved in maintaining blood pressure. This trace element is a minuteplayer in blood pressure control.

Copper

Copper is an essential mineral required by all living systems and is clas-sified as a trace element. Epidemiological studies of copper reflected con-flicting findings (64) in blood pressure control. Vivoli et al. (64) hypothesizedthat an imbalance in copper status may occur in the hypertensive patient.Support for this is found in the observation that norepinephrine synthesis(Table 2) includes the participation of copper in the catalytic mechanism oftyrosinase (66). Likewise, reduction in the synthesis of prostaglandin I2(Table 2) and an increase in endothelium-derived relaxing factor may repre-sent two other mechanisms that can influence blood pressure (64). The traceelement copper is an active participant in human hypertension.

Iron

Iron is a trace element and an essential nutrient. In the obstetrical liter-ature since 1971, Samuels et al. (67) recognized hemolysis as a complicationof pregnancy-induced hypertension (Table 1). Entman and Moore (68)demonstrated that serum ferritin levels are increased in toxemia of preg-nancy. The cause of the increase in serum of iron is unknown; however, itappears that an ongoing hemolytic reaction is responsible for the increasethat occurs in patients with pregnancy-induced hypertension (67). This traceelement is a participant in blood pressure control in the obstetrical patient.

TOXIC GROUP

Lead

In our contemporary urban society, there is an increasing exposure ofhumans to toxic elements. The important ones which have an effect onhuman blood pressure (Table 1) are lead, mercury, cadmium, thallium,barium, and arsenic. The element lead is an old toxic mineral and the most

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ubiquitous of the trace elements. In 1886, Lorimer (69) reported an associ-ation between lead exposure and the incidence of hypertension. A surveyin the United States between 1976 to 1980 concluded that there was a directand linear relationship between blood lead and blood pressure (70). Inexamining the NHANES-II survey, Harlan et al. (70) in 1985 found a directrelationship between blood lead levels and systolic and diastolic pressuresfor men and women, for black and white, and younger persons. Studies byBatuman et al. (71) suggested that a renal toxic reaction was responsible forthe hypertension (Table 1) and that increased tissue lead could be mobi-lized by chelating agents. In pregnancy, lead appears to have a hyperten-sive effect on blood pressure at the time of delivery but not in patients withpreeclampsia (69). Stern (72) reported that male adults exposed to 1000ppm of lead in soil will have an increase of 1 mm systolic pressure. Regard-ing mechanisms of action of lead on blood pressure, Sandstead et al. (73)observed that plasma renin and aldosterone levels (Table 2) are decreasedin lead poisoning. This toxic element’s effect on blood pressure can be pre-ventable through public health measures.

Mercury

The toxic effects of mercury have been known since the Middle Agesand has been used for 3000 yr in medicine and industry, although most med-ical uses have been discontinued. Three forms of mercury are the organic,inorganic, and the elemental. Both the organic and the inorganic mayundergo environmental transformation. The elemental mercury may be oxi-dized to inorganic divalant mercury. Mining, smelting, and industrial dis-charge have been factors in environmental contamination (74). Harvey (75)reported that excessive amounts of mercury in the body can lead to hyper-tension (Table 1). In 1970, El-Sadik and El-Dakhakhny (76) studied 68 work-ers exposed to mercury along with 10 who were not exposed. Of those 68exposed, 30% were hypertensive. Shiryaev (77), the following year, foundthat 15% of a separate group of workers exposed to mercury had hyperten-sion. El-Sadik and El-Dakhakhny (76) concluded that although not statisti-cally significant, a higher role of hypertension among those exposed cannotignore mercury’s role. Barni et al. (78) reported that mercury poisoningcauses arteriosclerosis mainly in the kidneys, resulting in hypertension. Mer-cury poisoning can be treated with metal-chelating agents (75), which protectthe kidneys from the toxin and also lowers the blood pressure. Huggins et al.(79) found that possibly angiotensin-converting enzyme activity (Table 2) isstrongly inhibited by mercury, which also could lower blood pressure. Thistoxic element’s effect can be prevented with adequate industrial controls.

Barium

Barium is a nonessential trace element. In 1971, Roza and Berman(80) reported a clinical array of complications after ingestion of bariumsalts, including hypertension (Table 1). Brenniman et al. (81) found that



drinking water in high-barium areas (2–10 mg/L) resulted in higher car-diovascular deaths compared to low-barium areas. Barium participatesin the release of adrenal catecholamine hormones (Table 2), epinephrine,and norepinephrine (82), which could be related to its effect on bloodpressure. Chronic ingestion of barium was found to elevate systolicblood pressure in animals; however, in 1989, Perry et al. (83) concludedthat ingestion of abnormal amounts of barium induced an increase insystolic blood pressure; however, there is no convincing evidence thatexposure to barium produces hypertension in human beings. Neverthe-less, prevention of this toxic trace element from entering drinking wateris paramount.

Cadmium

Cadmium is a modern toxic metal enrolled as an element in 1817 andis a byproduct of zinc and lead mining and smelting. There has been diffi-culty in relating cadmium to human hypertension. In 1965, Schroeder (84)described finding a high mean renal cadmium level in subjects dying ofhypertension as compared to other causes of death. Human postmortemdata by Schroeder et al. (85) described elevated levels, whereas Syverson etal. (86) reported no significant difference (Table 1) in cadmium levels. Mor-gan (87), on the other hand, reported no support for the hypothesis thatcadmium concentration might be related to hypertension. An epidemiolog-ical survey on smelter workers revealed that blood pressure was elevatedby low-level exposure to cadmium; contrariwise, blood pressure was sup-pressed by high levels of cadmium exposure (88). The action of cadmium isnot known but an association with sodium retention, increased contractileresponse to aortic strips, and coronary vasoconstriction have beendescribed (88). The role of cadmium in human hypertension is not clear,although extending experimental data (89) may help prove the element’sinvolvement in the pathogenesis of hypertension.

Arsenic

Arsenic exposure occurred in the 19th-century literature by meansof environmental, medicinal, and occupational situations. Arsenicalcompounds are either organic or inorganic in form and each is trivalentor pentavalent. The trivalent compounds of arsenic are principally thetoxic forms. Inorganic arsenic is released into the environment througha number of sources, such as copper, lead, and zinc. Smelting is moretoxic than the organic form, which is toxic mainly through the ingestionof high concentrations of arsenic in drinking water (90). Some organicforms of arsenic are nontoxic and are used in pharmaceuticals and foodadditives (91).

Long-term exposure to arsenic was reported by Chen et al. (92) in 1989,indicating induced hypertension (Table 1) in Taiwanese patients who hadbeen exposed to the element in drinking water. In a 27-yr follow-up of

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arsenic ingestion, an American study by Upshaw and Clayborn (93) foundthat hypertension did not occur until 11 yr later and was well controlledwith a β-blocker. Possible mechanisms of the action of arsenic-related hyper-tension may be the result of renal and neurological defects induced by thismetal and its hindrance of normal enzymatic functions (92). Education bypublic health measures could prevent occurrences of arsenic intoxication.

Thallium

Thallium is one of the minor elements but one of the most toxic met-als. In the late 19th century, thallium salts were used to treat a variety ofmedical conditions (94), but in 1972, Bank et al. (95) reported that excessiveamounts of thallium in the body can result in hypertension (Table 1). Acommon source of thallium poisoning is often from ingestion of rodenti-cides. Most of the element is contained in the intracellular compartmentand is then excreted through urine and feces. Thallium intoxication resultsin diastolic hypertension (95), which gradually returns to normotensionwith potassium chloride treatment. Catecholamine metabolism (Table 2)may be altered in thallium intoxication (96), which might explain its bloodpressure effects. This toxic element has been controlled by reformulationof rodenticides.

MISCELLANEOUS GROUP

Lithium

Lithium is a monovalent cation, a member of the alkali metal group.The older literature reported in the early 1900s that lithium salts (Table 1)cause a fall in blood pressure (97). Lithium chloride was used in the 1940s(97) as a flavoring for salt substitutes, in low-sodium diets, for treatingcongestive heart failure and hypertensive patients (98). In a 1984 surveyby Hansen and Andisen of 123 patients with lithium intoxication, only 2were reported as having mild hypertension (99). Lithium and salt com-pete proximally for reabsorption facilitating naturesis and blood pressurereduction. On the other hand, Michaeli et al. (100) reported severe hyper-tension (Table 1) in a normotensive patient following acute lithium car-bonate intoxication (100), probably resulting from renal injury (75). Apossible explanation for the contradictory reports may be seen in themanagement of a depressive disorder in a hypertensive patient usinglithium carbonate and a tricyclic agent for depression. This treatmentregime resulted in blood pressure reduction: however, upon reducing thedose of the tricyclic medication, an increase in blood pressure followed(101). Lithium administration has been shown to stimulate renin secretion(100), to increase the level of desiccated catechol metabolism (Table 2),and to decrease norepinephrine levels (102) as possible mechanisms of



action. Through pharmaceutical diligence and patient education, lithiumtoxicity can be prevented.

Selenium

In the last decade, selenium has gained major attention as a nutrition-ally essential trace element, although its potential environmental poison-ous effects have been known for 50 yr (74). Selenium forms in soluablecomplexes with arsenic, cadmium, copper, mercury, and silver and con-structively becomes an antidote to their individual toxic effects (74). Inter-actions of selenium with other minerals is important because there isexperimental evidence that selenium can reduce the hypertensive effect ofcadmium and mercury (103).

The association of selenium to cardiovascular disease was docu-mented by Keshan disease, an endemic cardiomyopathy caused by a lowerselenium content in a diet of maize and rice grown in areas of Japan (104).This metalloid has been characterized as having three faces, with reportsof a progressive fall, a considerable rise, and no change in blood pressure(Table 1). This confusion might be explained by the fact that very minutedoses of selenium compounds have no effect on blood pressure, whereaslarger doses produce a fall in pressure, although a rise in pressure isinduced with potasium selenocyanate (105).

Conversely, Tuomilehto (106) found that low dietary intake of sele-nium raised blood pressure. Other facets, as described in the Japanesestudy (107), include sexual differences where selenium levels correlatedwith blood pressure in normotensive males but not with females. Han andZhou (108) used selenium supplementation for the prevention and treat-ment of pregnancy-induced hypertension. In 1991, Perry et al. (109) foundthat selenium concentrations were higher in kidneys from hypertensivesubjects as compared to normotensive ones. Physiological studies revealedthat a rise in blood pressure (Table 2) was suppressed by sodium seleniteafter angiotensin II infusion (110). Another mechanism of seleniuminvolves the prostaglandin system (106). Selenium toxicity can be con-trolled by pharmaceutical and public health measures, because being anessential nutrient, dietary intake of selenium must be adequate.

CONCLUSIONS

The observations that normal and abnormal concentrations and/orimbalances of these elements may influence blood pressure have been pre-sented through the study of blood pressure in the human. Of the known 28elements (1) that might effect blood pressure in man, only 15 are identifiedin the literature, and these have reduced the periodic table to a reasonablenumber of elements to consider in the control of human blood pressure.

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Certainly, a single element does not result in a universal effect on bloodpressure; however, interactions between various elements and systems mayaffect blood pressure control. Further epidemiological and clinical studies ofthese elements will clarify the position of each and have significant implica-tions for the prevention and management of human blood pressure.

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