Showing papers in "Environmental Health Perspectives in 1988"
TL;DR: Phytochemical options exist by which plants can modulate the fertility of the other major group of plant predators, vertebrate herbivores, and thereby reduce cumulative attacks by those Herbivores.
Abstract: Plants have physical and chemical mechanisms for defense from attack by animals. Phytochemical defenses that protect plants from attack by insects include antifeedants, insecticides, and insect growth regulators. Phytochemical options exist by which plants can modulate the fertility of the other major group of plant predators, vertebrate herbivores, and thereby reduce cumulative attacks by those herbivores. The success of such a defense depends upon phytochemical mimicry of vertebrate reproductive hormones. Phytoestrogens do mimic reproductive hormones and are proposed to be defensive substances produced by plants to modulate the fertility of herbivores.
118 citations
TL;DR: The relationship of blood lead and blood pressure at relatively low levels commonly observed in the general population is confirmed by analysis of data from the National Health and Nutrition Examination Survey II.
Abstract: Numerous observations have indicated a relationship between moderate or heavy lead exposure and high blood pressure. To determine whether low-level lead exposure is related to blood pressure in the U.S. population, we analyzed data from the National Health and Nutrition Examination Survey II for persons 12 to 74 years of age. Significant correlations were found between blood lead and blood pressure for each race-gender group, and blood lead levels were significantly higher in groups with high diastolic blood pressure (greater than 90 mm Hg). Multiple stepwise regression models were developed to predict blood pressure. After adjusting for age, race, and body mass index, blood lead levels were significantly related to systolic and diastolic pressures in males but not in females. These findings and those from other studies confirm the relationship of blood lead and blood pressure at relatively low levels commonly observed in the general population. The strength and importance of this relationship require further study through epidemiologic and metabolic investigations.
112 citations
TL;DR: It can be concluded that lead over a wide range of exposure intensities can induce significant changes in the function of the cardiovascular system, and evidence points to the involvement of multiple sites of action.
Abstract: Chronic and acute lead poisoning cause overt, clinical symptoms of cardiac and vascular damage with potentially lethal consequences. Morphological, biochemical, and functional derangements of the heart have all been described in patients following exposure to excessive lead levels. Disturbances in cardiac electrical and mechanical activity and postmortem evidence of morphological and biochemical derangements of the myocardium have all been reported following excessive exposure to lead in humans. In addition, signs of vascular degeneration, abnormal vascular smooth muscle function, and altered vessel compliance have been described in humans chronically and acutely exposed to toxic lead levels. Similar cardiovascular complications have been detected following excessive lead exposure in experimental animals. Myocarditis, electrocardiographic disturbances, heightened catecholamine arrhythmogenicity, altered myocardial contractile responsiveness to inotropic stimulation, degenerative structural and biochemical changes affecting the musculature of the heart and vasculature, hypertension, hypercholesterolemia, atherosclerosis, and increased vascular reactivity to alpha-adrenergic agonists have been among the reported cardiovascular disturbances linked to lead poisoning. Less certain are the cardiovascular effects of subclinical lead poisoning. Although controversial, chronic low-level lead exposure has been linked to hypertension and other cardiovascular disturbances in both clinical and experimental studies. In general, it can be concluded that lead over a wide range of exposure intensities can induce significant changes in the function of the cardiovascular system. Evidence points to the involvement of multiple sites of action. Cardiac and vascular sites, as well as sites within the central nervous system, have all been implicated in the sequelae of cardiovascular effects. The exact pathogenic mechanisms that underlie the actions of lead in the cardiovascular system, however, have yet to be elucidated definitively.(ABSTRACT TRUNCATED AT 250 WORDS)
105 citations
TL;DR: There exists a very weak but statistically significant positive association between blood lead and both systolic and diastolic blood pressure, and it is unlikely that any consequent association between lead and cardiovascular disease could be demonstrated from prospective epidemiological studies.
Abstract: The relationship between blood lead concentration and blood pressure is examined in a survey of 7371 men aged 40 to 59 from 24 British towns. After allowance for relevant confounding variables, inc...
102 citations
TL;DR: The robustness of the previously reported association between blood lead and blood pressure in adult males is examined, finding that the relationship remains strong and is essentially unchanged in tests that include nutritional factors and demographic factors, alone or together, or in Tests that include insignificant terms.
Abstract: A large body of experimental data has shown that lead raises blood pressure and increases responsiveness to alpha-adrenergic agonists in rats and pigeons. These studies suggest the need to look for a similar relationship in humans. This paper examines the robustness of the previously reported association between blood lead and blood pressure in adult males. The association remains strong and is essentially unchanged in tests that include nutritional factors and demographic factors, alone or together, or in tests that include insignificant terms. The relationship was not confounded by age; it held for all adult men in the 20-45 age group, the 40-59 age group, and the 46-74 age group. Interaction terms for 25 30-year age groups (20-49, 21-50,. . . , 45-74) were all insignificant, indicating no difference in the relationship by age. The relationship is also robust to the inclusion of a time trend to account possible omitted time-varying factors, and it held in a model that controlled for possible site effects. Given the strong experimental evidence, the relationship is likely causal.
78 citations
TL;DR: Findings suggest effects of lead exposure at lower blood lead concentrations than those concentrations that have previously been linked with increases in blood pressure.
Abstract: San Francisco bus drivers have an increased prevalence of hypertension. This study examined relationships between blood lead concentration and blood pressure in 342 drivers. The analysis reported in this study was limited to subjects not on treatment for hypertension (n = 288). Systolic and diastolic pressures varied from 102 to 173 mm Hg and from 61 to 105 mm Hg, respectively. The blood lead concentration varied from 2 to 15 micrograms/dL. The relationship between blood pressure and the logarithm of blood lead concentration was examined using multiple regression analysis. Covariates included age, body mass index, sex, race, and caffeine intake. The largest regression coefficient relating systolic blood pressure and blood lead concentration was 1.8 mm Hg/ln (micrograms/dL) [90% C. I., -1.6, 5.3]. The coefficient for diastolic blood pressure was 2.5 mm Hg/ln (micrograms/dL) [90% C. I., 0.1, 4.9]. These findings suggest effects of lead exposure at lower blood lead concentrations than those concentrations that have previously been linked with increases in blood pressure.
77 citations
TL;DR: The data suggest a biphasic dose response of lead, and establishment of an appropriate animal model to study blood pressure effects of lead will require careful assessment of dietary interactions with lead, unstressed blood pressure monitoring with standardized techniques, and documentation of biologically effective lead burden.
Abstract: Information obtained in a number of experimental studies conducted over the last 40 years on the effects of lead on blood pressure is reviewed. Differences in animal species, age at beginning of exposure, level of lead exposure, indices of lead burden, and blood pressure effects of each study are reported. In several of the high-dose experiments, hypertension was observed, but nephrotoxicity of lead may have contributed to its development. Moreover, in other high-dose experiments, no hypertension was observed, and in at least one experiment, the evidence suggested that lead could reduce an elevated blood pressure. In contrast, the lower dose experiments consistently demonstrated a hypertensive effect. Overall, the data suggest a biphasic dose response. Establishment of an appropriate animal model to study blood pressure effects of lead will require careful assessment of dietary interactions with lead, unstressed blood pressure monitoring with standardized techniques, and documentation of biologically effective lead burden. Future research should examine lead exposure at more environmentally appropriate levels in order to determine the validity of associating this pollutant with blood pressure effects in the human population.
72 citations
TL;DR: The results of a study on male Sprague-Dawley rats that received 0, 15, 30, and 60 micrograms/mL of lead in drinking water for 18 months were reported in this paper.
Abstract: Previous human studies demonstrated that lead exposure may modify the metabolism of catecholamines and of hormones controlled by the hypothalamo-pituitary axis and may affect the kallikrein-kinin system. This paper reports unpublished data on the plasma renin activity of lead-exposed workers; these results are in agreement with those of previous human and experimental studies suggesting that the synthesis or release of renin is increased after short and moderate exposure to inorganic lead and reduced whenever the exposure is prolonged. Previous experimental investigations demonstrated that lead may act on the cardiovascular system, with effects on the renin-angiotensin system, on the reactivity to stimulation of peripheral catecholaminergic receptors, on sympathetic and vagal tone, and on reactivity to the stimulation of baroreceptors. This paper reports the results of a study on male Sprague-Dawley rats that received 0, 15, 30, and 60 micrograms/mL of lead in drinking water for 18 months. Blood pressure was increased in the rats receiving 30 and 60 ppm of lead; cardiac inotropism was augmented only in those receiving the higher dose of the metal, and heart rate was not modified. Cardiovascular responses to agonists indicated that lead exposure affects the renin-angiotensin system and induces sympathetic hyperactivity by acting on central and peripheral sympathetic junctions increasing the responsiveness to stimulation of alpha 2-adrenoreceptors and by increasing the reactivity to stimulation of cardiac and vascular beta-adrenergic and dopaminergic receptors. The cAMP-dependent availability of Ca2+ for contractile mechanisms of the cardiovascular muscle cells was affected by lead.
70 citations
TL;DR: It is proposed that a cellular component of the action of lead to increase vascular reactivity may relate to the role of protein kinase C in smooth muscle contraction.
Abstract: Considerable controversy exists concerning the possible role of lead in the etiology of human hypertension. In animal studies, there is convincing evidence that lead alters cardiovascular responsiveness; rats drinking water containing 100 ppm lead develop a chronic, significant 15 to 20 mm Hg elevation in systolic blood pressure. Pressor responsiveness to catecholamines is enhanced in animals chronically exposed to lead, and the responsiveness of isolated vascular smooth muscle to adrenergic agonists is increased in rats with lead-induced hypertension. Experimental evidence suggests that alterations in the cellular mechanisms that regulate intracellular calcium concentration may contribute to the abnormal vascular function in lead-induced hypertension. Recent work in our laboratory indicates that increased vascular reactivity in genetic hypertension is associated with altered activity of the protein kinase C branch of the calcium messenger system. Contractile responses to lead in rabbit mesenteric artery are potentiated by activators (phorbol esters) of this enzyme complex, and a selective inhibitor of protein kinase C inhibited contractions induced by lead. Based on these results, it is proposed that a cellular component of the action of lead to increase vascular reactivity may relate to the role of protein kinase C in smooth muscle contraction.
59 citations
TL;DR: The hypotension usually seen in most animal studies is thought to be a primary cause of CNS damage resulting from acute CO poisoning, yet the exact mechanism remains unproven in both animals and humans, as does the way in which CO produces hypotension.
Abstract: Historically, and at present, carbon monoxide is a major gaseous poison responsible for widespread morbidity and mortality. From threshold to maximal nonlethal levels, a variety of cardiovascular changes occur, both immediately and in the long term, whose homeostatic function it is to renormalize tissue oxygen delivery. However, notwithstanding numerous studies over the past century, the literature remains equivocal regarding the hemodynamic responses in animals and humans, although CO hypoxia is clearly different in several respects from hypoxic hypoxia. Factors complicating interpretation of experimental findings include species, CO dose level and rate, route of CO delivery, duration, level of exertion, state of consciousness, and anesthetic agent used. For example, tachycardia is commonly observed, although bradycardia also can result from myocardial and/or central nervous system (CNS) hypoxemia at high carboxyhemoglobin (COHb) saturations, as can electrocardiographic abnormalities. Augmented cardiac output usually observed with moderate COHb may be compromised in more severe poisoning for the same reasons, such that regional or global ischemia result. The hypotension usually seen in most animal studies is thought to be a primary cause of CNS damage resulting from acute CO poisoning, yet the exact mechanism(s) remains unproven in both animals and humans, as does the way in which CO produces hypotension. This review briefly summarizes the literature relevant to the short- and long-term hemodynamic responses reported in animals and humans. It concludes by presenting an overview using data from a single species in which the most complete work has been done to date.
57 citations
TL;DR: The incidences of all primary neoplasms in the testes and accessory reproductive organs of 51,230 male Fischer 344 (F344) rats and 46,752 male B6C3F1 mice were obtained from the pathology data base of more than 300 long-term toxicity/carcinogenicity studies performed for the National Toxicology Program.
Abstract: The incidences of all primary neoplasms in the testes and accessory reproductive organs of 51,230 male Fischer 344 (F344) rats and 46,752 male B6C3F1 mice were obtained from the pathology data base of more than 300 long-term toxicity/carcinogenicity studies performed for the National Toxicology Program. The overall incidence of reproductive system neoplasms in male F344 rats was 81.5%. The most common neoplasms were interstitial cell adenoma of the testis (76.6%), adenoma/carcinoma of the preputial glands (2.9%), mesothelioma of the tunica vaginalis (1.5%), and adenoma of the prostate gland (0.3%). The combined incidence (0.1%) of 59 other rare neoplasms consisted of 18 different types that occurred with a frequency of 4 or less. In contrast to the rats, male B6C3F1 mice had a low overall incidence (0.6%) of neoplasms in reproductive organs. The most common neoplasm was the interstitial cell adenoma (0.4%). Thirty additional types of neoplasms were identified. Each of these uncommon neoplasms occurred at a frequency of 12 or less with an overall combined incidence of 0.2%. Morphological features are described for neoplasms in the rat and mouse, and criteria are presented for differentiation of testicular interstitial cell adenoma, prostatic adenoma, and mesothelioma from hyperplastic changes.
TL;DR: The rabbit is the smallest and least expensive laboratory animal in which serial semen samples can be obtained for morphologic, biochemical, and fertility evaluation and is an extremely valuable model for studying the effects of chemicals or other stimuli on the male reproductive system.
Abstract: The rabbit is the smallest and least expensive laboratory animal in which serial semen samples can be obtained for morphologic, biochemical, and fertility evaluation. The female rabbit has a predictable reproductive cycle and can be artificially inseminated with a known amount of sperm during fertility testing. These advantages make the rabbit an extremely valuable model for studying the effects of chemicals or other stimuli on the male reproductive system. Quantitative evaluation of the testis, semen, and accessory reproductive organs is important in order to detect subtle effects of a chemical on reproductive capacity. Evaluation of testis size, serum hormone concentrations, and the number, morphology, motility, and fertility of sperm in the ejaculate can be performed serially in the live rabbit. Weights of testes and accessory reproductive organs, estimates of daily sperm production, and histomorphometric data on the seminiferous epithelium can be obtained after sacrifice. Multinucleated spermatids, focal tubular hypospermatogenesis, swelling of spermatocytes, and cytoplasmic vacuoles in Sertoli's cells occur commonly in testes of control rabbits. These changes may be confused with toxic lesions. The incidence of multinucleated spermatids may be increased by stress associated with handling or the environment. Histomorphometric evaluation may be required to prove that a test compound has an adverse effect on the male reproductive system.
TL;DR: In a longitudinal study of lead foundry workers, an association was found between short-term changes in an individual's blood lead level and contemporary changes in diastolic pressure; this remained significant after allowance for age (or time) trends and for effects attributable to changes in body weight.
Abstract: Analysis of data collected during the Canada Health Survey of 1978-1979 indicated a positive relationship between blood lead and blood pressure, but so weak that the range of lead-related variation...
TL;DR: Hyperplasia of the rete testis and Müllerian duct structures were found in many of the DES-treated male mice, as was a low but significant number of reproductive tract neoplasms.
Abstract: Cryptorchidism and retention of Mullerian duct structures occur with high frequency among the male offspring of CD-1 mice treated with 100 micrograms diethylstilbestrol/kg body weight on days 9 through 16 of pregnancy. Hyperplasia of the rete testis and Mullerian duct structures were found in many of the DES-treated male mice, as was a low but significant number of reproductive tract neoplasms.
TL;DR: The human data are consistent with the tentative hypothesis that lead-exposed persons may have higher PRA than normal during the early periods of modest exposure but normal or depressed PRA following more chronic severe exposures.
Abstract: This paper reviews the chronic effects of lead exposure on the renin-angiotensin system in experimental animals and human beings. In rats, when lead exposure is begun several weeks after birth in doses that cause blood lead concentrations (PbB) of 30 to 40 micrograms/dL, the result is an increase in basal plasma renin activity (PRA) and renal renin concentration, with no change in the metabolic clearance of renin; this is presumptive evidence for increased renin secretion. PRA is also increased in 1-month-old animals whose exposure to lead (in doses that raise PbB to 9 micrograms/dL) was begun in utero. In contrast, older animals whose exposure was begun in utero manifest no change or a decrease in their PRA and renal renin concentration. Regardless of when the exposure is begun, lead can decrease the plasma concentration of angiotensin II at any given PRA, but the dose required for this effect is highly variable. The hypertension induced by lead exposure is associated with low PRA and a normal angiotensin II/PRA ratio. Chronic human exposure to lead also is associated with highly variable changes in PRA from study to study; it has been reported to be decreased under both basal and stimulated conditions, unchanged, or increased in a manner exponentially related to PbB. The human data are consistent with the tentative hypothesis that lead-exposed persons may have higher PRA than normal during the early periods of modest exposure but normal or depressed PRA following more chronic severe exposures. In a small preliminary study, blood lead concentration was found to be higher in high-renin hypertensive persons than in normotensive persons.
TL;DR: Rats exposed to lead in amounts comparable to the environmental exposure of many Americans had an average elevation in systolic pressure comparable to that of human beings with essential hypertension.
Abstract: Groups of 15 to 18 female weanling Long-Evans rats fed a rye-based diet low in lead (0.25 ppm) were exposed to 0.1, 1.0, and 5.0 ppm lead in drinking water. No suggestion of clinical lead toxicity was recognized. Systolic pressures were measured at 3-month intervals after weaning. The groups of lead-exposed animals had consistently and significantly higher average pressures than control animals, the increase approximating 15 mm Hg. With the lowest lead exposure (0.1 ppm), the increase in average pressure was gradual, being half minimal at 3 months and requiring 1 year to become maximal. After 1 year, half of these rats had pressures from 0 to 10 mm Hg above the control average; 40, 20, and 10% had pressures that were 20, 30, and 40 mm Hg, respectively, above the control average. Thus, rats exposed to lead in amounts comparable to the environmental exposure of many Americans had an average elevation in systolic pressure comparable to that of human beings with essential hypertension.
TL;DR: The task of this symposium is of public health importance, as relatively minor changes in the distribution and mean levels of blood pressure in populations are associated with major morbidity and mortality consequences.
Abstract: An overview of the epidemiology of blood pressure is presented as background for the International Symposium of Blood Lead-Blood Pressure Relationships. The correlates of blood pressure distributions in populations are varied and numerous. They have to be considered as either potential confounders or modifiers of any blood pressure-blood lead relationship detected. The relation of blood pressure to cardiovascular morbidity and mortality emphasizes the importance of detecting and elucidating any possible causal association of blood lead with blood pressure at low levels. The task of this symposium is of public health importance, as relatively minor changes in the distribution and mean levels of blood pressure in populations are associated with major morbidity and mortality consequences.
TL;DR: This report summarizes key exchanges of information during discussions after individual papers were presented or during separate discussion sessions about the extant literature on lead and blood pressure relationships.
Abstract: The International Symposium on Lead-Blood Pressure Relationships was held in Chapel Hill, NC, April 27-29, 1987, with sponsorship from the Councils on Hypertension and Epidemiology of the American Heart Association; the Department of Epidemiology, University of North Carolina; the International Lead Zinc Research Organization; and the US Environmental Protection Agency. The program was structured so as to first present an overview of theories and findings in the general area of human hypertension and then to have speakers review the extant literature on lead and blood pressure relationships, including papers on the human observational studies of lead and human hypertension; related studies of lead and human hypertension; occupational studies of lead and hypertension, experimental studies of lead and hypertension; and papers presenting related information from work in progress. This report summarizes key exchanges of information during discussions after individual papers were presented or during separate discussion sessions. It also summarizes presentations by several speakers who declined to publish in these proceedings full-length papers on ongoing work.
TL;DR: In vitro, cytotoxicity appeared to be too variable for predictive purposes, though direct assay of fibrogenicity using the macrophage fibrogenic factor suggested that dust dose was more important than dust composition.
Abstract: Dust dose and composition do not appear to account wholly for changes in the prevalence of coal workers' pneumoconiosis in Europe. In certain coal pits high progression evidently occurred with relatively low dust exposure or vice versa, whereas progression in relation to dust levels might be variable. Exceptionally high quartz concentrations occur in coal mine dust when pneumoconiosis may progress with unusual rapidity. Under such circumstances lesions resembling silicotic nodules may be found, but with the customarily lower levels of quartz the pathological features assume the form characteristic of coal workers. Morphological changes in relation to dust content of human and animal lungs, as well as cellular behavior, have not accounted completely for the epidemiological findings. Considering all the pathological evidence helps explain the pathogenesis of pneumoconiosis and vagaries of progression. The origin of progressive massive fibrosis cannot be explained simply in terms of dust burden or immunological features, and the role of an infective factor cannot be dismissed. Moreover, lipid secretion by alveolar epithelium introduces a new element that could affect the development of simple and complicated pneumoconiosis. In vitro, cytotoxicity appeared to be too variable for predictive purposes, though direct assay of fibrogenicity using the macrophage fibrogenic factor suggested that dust dose was more important than dust composition. Assessing individual susceptibility presents serious obstacles.
TL;DR: After both univariate and multivariate analyses, a significant association was found between blood lead and blood pressure, and this relation was stronger for systolic than for diastolic blood pressure.
Abstract: Information about blood lead and other coronary heart disease risk factors was collected in 1977 among 152 men aged 57 to 76 years in the town of Zutphen, the Netherlands. Blood lead was determined...
TL;DR: In vivo tibial X-Ray-induced X-ray fluorescence is a more practical noninvasive technique for assessing bone lead, which should find widespread application as a diagnostic tool and for epidemiologic studies.
Abstract: There is considerable clinical evidence that excessive lead absorption causes renal failure with hypertension and predisposes individuals to hypertension even in the absence of detectable renal failure. Recent analyses of transiliac bone biopsies indicate that unsuspected elevated bone leads may reflect the cause (or contributing cause) of end-stage renal disease in 5% of the European dialysis population. In these patients, bone lead levels were four times higher than in unexposed cadavers (6 micrograms/g wet weight) and approximated levels found in lead workers (30 micrograms/g). At present, the most reliable index of the body lead burden is the CaNa2 EDTA lead mobilization test. In vivo tibial X-ray-induced X-ray fluorescence (XRF) is a more practical noninvasive technique for assessing bone lead, which should find widespread application as a diagnostic tool and for epidemiologic studies.
TL;DR: The overall average association between blood lead level and blood pressure was so minute that the only rational conclusion is that there is no evidence for this association to be found in the NHANES II data.
Abstract: In performing research for associations and relationships among the data thus far published from the NHANES II survey, only the data for the 64 communities involved may be used. The simple omission of a few essential data makes impossible any valid analysis from the data for the 20,325 individual respondents. In this research for associations between blood lead levels and blood pressure in NHANES II, the method of forward stepwise regression was used. This avoids the problem of inflated error rates for blood lead, maximizes the number of data analyzed, and minimizes the number of independent variables entered into the regression model, thus avoiding the pitfalls that previous NHANES II research of blood lead and blood pressure has fallen into when using backward stepwise regression. The results of this research for white male adults, white female adults, and black adults were contradictory and lacked consistency and reliability. In addition, the overall average association between blood lead level and blood pressure was so minute that the only rational conclusion is that there is no evidence for this association to be found in the NHANES II data.
TL;DR: The in vitro serum protein-binding characteristics of DEHP and MEHP are shown to be highly dependent upon, and proportional to, the lipid concentration of the serum, and these data indicate that the protein- binding characteristics of these compounds, in vitro, is somewhat more complex than previously reported.
Abstract: The metabolism and toxicity of the ubiquitous plasticizer, bis-(2-ethylhexyl) phthalate (DEHP), and its principal metabolite, mono-(2-ethylhexyl) phthalate (MEHP), have been extensively investigated. In an attempt to understand their disposition in man, we studied the in vitro serum protein-binding characteristics of these compounds, using ultracentrifugation and agarose gel electrophoresis. The association of DEHP and lipoproteins was shown to be highly dependent upon, and proportional to, the lipid concentration of the serum. It appears that more than half of the serum DEHP is bound to proteins with density greater than 1.21 g/mL when the concentration of cholesterol is below 300 mg/dL or the cholesterol and triglyceride total concentration is less than 600 mg/dL. As the cholesterol and triglyceride concentrations increase, the percent DEHP bound to VLDL, IDL, and LDL increases. MEHP is bound principally to nonlipoprotein constituents in the serum, and this binding distribution is unaffected by lipid concentration. The percent binding of DEHP and MEHP to individual proteins was also found to be unaffected by their concentrations in serum. These data indicate that the protein-binding characteristics of these compounds, in vitro, is somewhat more complex than previously reported.
TL;DR: Kinetics of inhibition of Na-K-ATPase by lead, ouabain, and natriuretic hormone was studied and it was revealed that NH is the most potent inhibitor of the enzyme system.
Abstract: Inhibition of vascular smooth muscle sodium-potassium-activated adenosine triphosphatase (Na-K-ATPase) has been postulated as a central mechanism in enhancing vascular contractility. In the present study, kinetics of inhibition of Na-K-ATPase by lead, ouabain, and natriuretic hormone (NH) was studied in a purified hog cerebral cortex enzyme preparation. Determination of I50 values for lead, ouabain, and NH revealed that NH is the most potent inhibitor of the enzyme system (0.8 x 10(-6) M ouabain equivalents). Kinetic analyses indicated that lead and NH exhibited different inhibitory mechanisms. The inhibition by lead was noncompetitive with respect to potassium and competitive with respect to sodium and MgATP. Natriuretic hormone was noncompetitive with respect to potassium, uncompetitive with respect to MgATP, and exhibited no inhibitory effect with respect to sodium. Synergism between lead and NH in the inhibition of Na-K-ATPase raises the possibility that lead may be a contributory factor in hypertension via this mechanism.
TL;DR: Results showed that blood lead no longer accounts for an increase in systolic blood pressure when Na+,K+ cotransport was taken into account; the same trend was observed with diastolic blood Pressure.
Abstract: Five red blood cell cation transport systems (RBCTS), together with blood lead level and blood pressure, were measured in 129 male adult subjects who were not occupationally exposed to lead or subsequent to a course of treatment for hypertension. Blood lead was positively related with systolic blood pressure, and to a lesser degree with diastolic blood pressure. Blood lead was found significantly negatively related to one of the RBCTS, Na+,K+ cotransport, and in addition, Na+,K+ cotransport appeared negatively related to blood pressure. Final results showed that blood lead no longer accounts for an increase in systolic blood pressure when Na+,K+ cotransport was taken into account; the same trend was observed with diastolic blood pressure. These findings suggest that a blood lead-related Na+,K+ cotransport impairment could explain the blood pressure increase observed to parallel the blood lead increase.
TL;DR: Multivariate analysis using a first-order autoregressive model revealed that after adjusting for previous systolic blood pressure, body mass index, age, and cigarette smoking, an elevated blood lead level was a significant predictor of subsequent systolics blood pressure.
Abstract: We examined the relationship of blood lead level to systolic and diastolic blood pressure in a longitudinal study of 89 Boston, MA, policemen. At the second examination blood lead level and blood pressure were measured in triplicate. Blood pressure measurements were taken in a similar fashion in years 3, 4, and 5. Multivariate analysis using a first-order autoregressive model revealed that after adjusting for previous systolic blood pressure, body mass index, age, and cigarette smoking, an elevated blood lead level was a significant predictor of subsequent systolic blood pressure. Bootstrap simulations of these models provided supporting evidence for the observed association. These data suggest that blood lead level can influence systolic blood pressure even within the normal range.
TL;DR: There were significant excess deaths for "other hypertensive disease" and "chronic nephritis" in both cohorts, the standardized mortality ratios (SMRs) being 320 and 475, respectively, for the former causes and 222 and 265 for the latter.
Abstract: This report is based on an analysis of deaths in 4519 battery plant workers and 2300 lead production or smelter workers during the years 1947 to 1980. Causes were coded to the seventh (1955) revision of the International Classification of Diseases. There were significant excess deaths for "other hypertensive disease" (444-447) and "chronic nephritis" (592-594) in both cohorts, the standardized mortality ratios (SMRs) being 320 and 475, respectively, for the former causes and 222 and 265 for the latter. Proportionate mortality analysis, which adjusted for race, also showed elevated ratios, 241 and 388 for the former causes and 296 and 186 for the latter. Deaths from other hypertension-related diseases did not show comparable excesses. Renal cancer deaths were fewer than expected, SMRs being 41 and 74, respectively.
TL;DR: This model offers a novel mechanism for prostatic carcinogenesis in which prostatic fibroblasts determine epithelial growth, androgen responsiveness, and tumorigenicity, and the potential importance of an epigenetic pathway in prostatic cancerogenesis.
Abstract: Inoculation of tumorigenic prostatic stroma and nontumorigenic prostatic epithelia into the subcutaneous space of syngeneic rats induced the development of carcinosarcoma The induced tumors, which were composed of a mixture of adenocarcinoma and fibrosarcoma, were androgen responsive This model offers a novel mechanism for prostatic carcinogenesis in which prostatic fibroblasts determine epithelial growth, androgen responsiveness, and tumorigenicity Our results emphasize the potential importance of an epigenetic pathway in prostatic carcinogenesis
TL;DR: No significant relationship between blood pressure and blood lead was detected in either of the population samples, and the regression coefficients suggest that if there were a real effect, then the mean difference in blood pressure per 10 micrograms difference in lead is likely to be 0.7 mm Hg in both systolic and diastolic pressures.
Abstract: The relationship between blood pressure and blood lead was examined in two population samples. One of these consisted of 1137 men aged 49 to 65 years, the other of 865 men and 856 women aged 18 to 64 years. Neither population had any known important exposure to lead, and the 95% ranges of blood lead levels were 6 to 26 micrograms/100 mL and 6 to 23 micrograms/mL in the men and 5 to 18 micrograms/100 mL in the women. No significant relationship between blood pressure and blood lead was detected in either of the population samples, and the regression coefficients suggest that if there were a real effect, then the mean difference in blood pressure per 10 micrograms difference in blood lead is likely to be 0.7 mm Hg in both systolic and diastolic pressures. In the survey of 1137 men, the rise in blood pressure was measured during the cold pressor test. This test is likely to be affected if lead were to affect neurogenic mediators of blood pressure. The mean change in systolic pressure was 24 mm Hg and the 95% range was -6 to 60 mm Hg, but there was no evidence of any association with blood lead level.
TL;DR: The Cadmibel Cooperative Study was designed to elucidate whether environmental exposure to lead and cadmium has any effect on blood pressure and renal function in the population at large as discussed by the authors.
Abstract: The question whether in the general population environmental exposure to lead and cadmium influences blood pressure after controlling for confounding factors remains debated. The environmental exposure of the Belgian population to both lead and cadmium is high as compared with other countries. The Cadmibel Cooperative Study was therefore designed to elucidate whether environmental exposure to lead and cadmium has any effect on blood pressure and renal function in the population at large. Before embarking on the large Cadmibel project, a small study was conducted. Blood pressure and the 24-hr urinary excretion of cadmium (CdU) and lead (PbU) were determined in a random 4% sample of the population of a small Belgian town. CdU averaged 0.27 micrograms/24 hr in 46 youths (mean age 14 +/- 3 years, +/- SD), increased with age, and was higher in 57 adult men (age 41 +/- 14 years), as compared with 59 adult women (age 39 +/- 14 years) (1.05 vs. 0.81 micrograms/24 hr; p less than 0.01). PbU averaged 5.8 micrograms/24 hr in youths and similarly increased with age; adult men excreted more lead than women (13.3 vs. 8.3 micrograms/24 hr; p less than 0.001). Among men, manual workers excreted more cadmium (1.4 vs. 0.8 micrograms/24 hr; p less than 0.05) but a similar amount of lead (7.0 vs. 6.9 micrograms/24 hr) as compared with office workers. In simple regression analysis, CdU was positively correlated with both systolic (r = 0.30; p less than 0.05) and diastolic (r = 0.38; p less than 0.01) blood pressure in women.(ABSTRACT TRUNCATED AT 250 WORDS)