Dataset Information

Chronic Low-Level Lead Exposure Increases Mesenteric Vascular Reactivity: Role of Cyclooxygenase-2-Derived Prostanoids.

ABSTRACT: Lead (Pb) exposure causes hazardous effects as hypertension and other cardiovascular diseases. We evaluated whether chronic Pb exposure alters the peripheral vascular resistance measuring the vascular reactivity of mesenteric resistance arteries in rats to identify the underlying mechanisms that are associated to the development of Pb-induced hypertension. Mesenteric resistance arteries from lead-treated and untreated Wistar rats (1st dose: 10 ?g/100 g; subsequent doses: 0.125 ?g/100 g, intramuscular, 30 days) were used. Contractile responses to phenylephrine increased, while acetylcholine and sodium nitroprusside-induced relaxation was not affected by lead treatment. Endothelium removal and inhibition of NO synthase by L-NAME similarly enhanced the response to phenylephrine in untreated and lead-treated rats. The antioxidants apocynin and superoxide dismutase (SOD) did not affect vasoconstriction in either group. The vascular expression of cyclooxygenase-2 (COX-2) protein increased after lead exposure. The respective non-specific or specific COX-2 inhibitors indomethacin and NS398 reduced more strongly the response to phenylephrine in treated rats. Antagonists of EP1 (SC19220), TP (SQ29548), IP (CAY10441) and angiotensin II type 1 (losartan) receptors reduced vasoconstriction only in treated rats. These conclusions present further evidence that lead, even in small concentration, produces cardiovascular hazards being an environmental contaminant that account for lead-induced hypertension.

SUBMITTER: Simoes MR

PROVIDER: S-EPMC7818781 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Chronic Low-Level Lead Exposure Increases Mesenteric Vascular Reactivity: Role of Cyclooxygenase-2-Derived Prostanoids.

Simões Maylla Ronacher MR Azevedo Bruna Fernandes BF Alonso María Jesús MJ Salaices Mercedes M Vassallo Dalton Valentim DV

Frontiers in physiology 20210107

Lead (Pb) exposure causes hazardous effects as hypertension and other cardiovascular diseases. We evaluated whether chronic Pb exposure alters the peripheral vascular resistance measuring the vascular reactivity of mesenteric resistance arteries in rats to identify the underlying mechanisms that are associated to the development of Pb-induced hypertension. Mesenteric resistance arteries from lead-treated and untreated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramus ...[more]

PMID: 33488395

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Project description:Lead (Pb) is neurotoxic and children are highly susceptible to this effect, particularly within the context of continuous low-level Pb exposure. A current major challenge is identification of children who may be uniquely susceptible to Pb toxicity because of genetic predisposition. Learning and memory are among the neurobehavioral processes that are most notably affected by Pb exposure, and modification of N-methyl-D-aspartate receptors (NMDAR) that regulate these processes during development are postulated to underlie these adverse effects of Pb. We examined the hypothesis that polymorphic variants of genes encoding glutamate receptor, ionotropic, NMDAR subunits 2A and 2B, GRIN2A and GRIN2B, exacerbate the adverse effects of Pb exposure on these processes in children. Participants were subjects who participated as children in the Casa Pia Dental Amalgam Clinical Trial and for whom baseline blood Pb concentrations and annual neurobehavioral test results over the 7 year course of the clinical trial were available. Genotyping assays were performed for variants of GRIN2A (rs727605 and rs1070503) and GRIN2B (rs7301328 and rs1806201) on biological samples acquired from 330 of the original 507 trial participants. Regression modeling strategies were employed to evaluate the association between genotype status, Pb exposure, and neurobehavioral test outcomes. Numerous significant adverse interaction effects between variants of both GRIN2A and GRIN2B, individually and in combination, and Pb exposure were observed particularly among boys, preferentially within the domains of Learning & Memory and Executive Function. In contrast, very few interaction effects were observed among similarly genotyped girls with comparable Pb exposure. These findings support observations of an essential role of GRIN2A and GRIN2B on developmental processes underlying learning and memory as well as other neurological functions in children and demonstrate, further, modification of Pb effects on these processes by specific variants of both GRIN2A and GRIN2B genes. These observations highlight the importance of genetic factors in defining susceptibility to Pb neurotoxicity and may have important public health implications for future strategies aimed at protecting children and adolescents from potential health risks associated with low-level Pb exposure.

Project description:BackgroundThe independent effect of lead exposure and parental education on children's neurocognition is well-documented. However, few studies have examined the combined effect of childhood lead exposure and parental education on adolescent neurocognition, especially in China.ObjectiveExamine both the combined and interactive effect of childhood blood lead levels (BLLs) and parental education on early adolescent neurocognition.Methods417 children from a longitudinal cohort study in Jintan, China had BLLs measured at 3-5 years and 12 years, parental education levels assessed at 3-5 years, and neurocognitive outcomes tested at 12 years.ResultsBLLs at 3-5 years were inversely associated with adolescent IQ (β -0.55 95% CI: -0.97, -0.13) but not working memory (β -0.06 95% CI: -0.23, 0.11) and parental education was positively associated with adolescent IQ (β 0.68 95% CI: 0.19, 1.17) and working memory (β 0.24 95% CI: 0.04, 0.44). BLLs and parental education evidenced combined effects on neurocognition, where children with higher BLLs and lower fathers' education had mean IQ scores 7.84 (95% CI: -13.15, -2.53) points lower than children with lower BLLs and higher fathers' education. There were significant associations between parental education and working memory, however, not with BLLs. The interaction between mother and father high school education and BLLs was insignificant for effects on IQ and working memory.SignificanceChildhood lead exposure and parental education levels have a combined and long-term impact on IQ, evidence that may partially explain disparities in lead exposure associated outcomes and highlight those children at greatest risk for neurocognitive deficits.Impact statementChildren continue to be exposed to low-levels of environmental lead in China and globally, warranting examination of the impact of such exposures. This paper demonstrates that even relatively low-level lead exposure in early childhood significantly influences adolescent neurocognitive functioning. Furthermore, co-existing social determinant of health-related variables, measured here as parental education, have a combined impact on neurocognition. These results highlight children at greater risk for neurocognitive deficits and demonstrate the need to examine the influence of lead exposure within the broader socio- ecological environment, as these factors work in tandem to influence longer-term neurocognitive outcomes.

Dataset Information

Chronic Low-Level Lead Exposure Increases Mesenteric Vascular Reactivity: Role of Cyclooxygenase-2-Derived Prostanoids.

Publications

Chronic Low-Level Lead Exposure Increases Mesenteric Vascular Reactivity: Role of Cyclooxygenase-2-Derived Prostanoids.

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