Limits...
Low-level lead exposure increases systolic arterial pressure and endothelium-derived vasodilator factors in rat aortas.

Fiorim J, Ribeiro Júnior RF, Silveira EA, Padilha AS, Vescovi MV, de Jesus HC, Stefanon I, Salaices M, Vassallo DV - PLoS ONE (2011)

Bottom Line: Lead treatment had the following effects: increase in systolic blood pressure (SBP); reduction of contractile response to phenylephrine (1 nM-100 µM) of aortic rings; unaffected relaxation induced by acetylcholine (0.1 nM-300 µM) or sodium nitroprusside (0.01 nM-0.3 µM).This effect is accompanied by increased p-eNOS, iNOS protein expression and Na(+)/K(+)-ATPase functional activity.These factors might be a compensatory mechanism to the increase in SBP.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Espírito Santo, Brazil.

ABSTRACT
Chronic lead exposure induces hypertension and alters endothelial function. However, treatment with low lead concentrations was not yet explored. We analyzed the effects of 7 day exposure to low lead concentrations on endothelium-dependent responses. Wistar rats were treated with lead (1st dose 4 µg/100 g, subsequent dose 0.05 µg/100 g, i.m. to cover daily loss) or vehicle; blood levels attained at the end of treatment were 9.98 µg/dL. Lead treatment had the following effects: increase in systolic blood pressure (SBP); reduction of contractile response to phenylephrine (1 nM-100 µM) of aortic rings; unaffected relaxation induced by acetylcholine (0.1 nM-300 µM) or sodium nitroprusside (0.01 nM-0.3 µM). Endothelium removal, N(G)-nitro-L-arginine methyl ester (100 µM) and tetraethylammonium (2 mM) increased the response to phenylephrine in treated rats more than in untreated rats. Aminoguanidine (50 µM) increased but losartan (10 µM) and enalapril (10 µM) reduced the response to phenylephrine in treated rats. Lead treatment also increased aortic Na(+)/K(+)-ATPase functional activity, plasma angiotensin-converting enzyme (ACE) activity, protein expression of the Na(+)/K(+)-ATPase alpha-1 subunit, phosphorylated endothelial nitric oxide synthase (p-eNOS), and inducible nitric oxide synthase (iNOS). Our results suggest that on initial stages of lead exposure, increased SBP is caused by the increase in plasma ACE activity. This effect is accompanied by increased p-eNOS, iNOS protein expression and Na(+)/K(+)-ATPase functional activity. These factors might be a compensatory mechanism to the increase in SBP.

Show MeSH

Related in: MedlinePlus

Potassium-induced relaxation in aortic rings from untreated (CT) and lead-treated (Pb+2) rats previously incubated in a K+-free medium and contracted with phenylephrine before and after incubation with 100 µM ouabain (A).Densitometry analyses of the western blots for the alpha-1 subunit (B) and alpha-2 subunit (C) in aortas from untreated (CT) and lead-treated rats (Pb+2). Representative blots are also shown. *P<0.05 (CT vs. Pb+2) by Student's t-test or two-way ANOVA followed by a Bonferroni test. #P<0.05 (CT OUA vs. Pb+2 OUA) by two-way ANOVA followed by a Bonferroni test. Number of animals used is indicated in parentheses.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3045404&req=5

pone-0017117-g006: Potassium-induced relaxation in aortic rings from untreated (CT) and lead-treated (Pb+2) rats previously incubated in a K+-free medium and contracted with phenylephrine before and after incubation with 100 µM ouabain (A).Densitometry analyses of the western blots for the alpha-1 subunit (B) and alpha-2 subunit (C) in aortas from untreated (CT) and lead-treated rats (Pb+2). Representative blots are also shown. *P<0.05 (CT vs. Pb+2) by Student's t-test or two-way ANOVA followed by a Bonferroni test. #P<0.05 (CT OUA vs. Pb+2 OUA) by two-way ANOVA followed by a Bonferroni test. Number of animals used is indicated in parentheses.

Mentions: We hypothesized that an increase in the Na+/K+-ATPase activity might be causing the reduction in vascular reactivity after phenylephrine treatment in the aortas from lead-treated rats. The activity of the sodium pump, which was evaluated by the potassium-induced relaxation curves before 100 µM ouabain incubation, increased in aortic rings from treated rats (Figure 6). Preincubation of intact segments with ouabain (100 µM) for 30 min in K+-free medium induced an increase in vascular tone in the aortas from both groups, but the increase was smaller in the last concentration of segments from lead-treated rats (Figure 6 A). In addition to this finding, the protein expression of the Na+/K+-ATPase alpha-1 subunit increased after lead treatment (Figure 6 B). However, the protein expression of the alpha-2 subunit of Na+/K+-ATPase was similar in the aortas from untreated and lead-treated rats (Figure 6 C).


Low-level lead exposure increases systolic arterial pressure and endothelium-derived vasodilator factors in rat aortas.

Fiorim J, Ribeiro Júnior RF, Silveira EA, Padilha AS, Vescovi MV, de Jesus HC, Stefanon I, Salaices M, Vassallo DV - PLoS ONE (2011)

Potassium-induced relaxation in aortic rings from untreated (CT) and lead-treated (Pb+2) rats previously incubated in a K+-free medium and contracted with phenylephrine before and after incubation with 100 µM ouabain (A).Densitometry analyses of the western blots for the alpha-1 subunit (B) and alpha-2 subunit (C) in aortas from untreated (CT) and lead-treated rats (Pb+2). Representative blots are also shown. *P<0.05 (CT vs. Pb+2) by Student's t-test or two-way ANOVA followed by a Bonferroni test. #P<0.05 (CT OUA vs. Pb+2 OUA) by two-way ANOVA followed by a Bonferroni test. Number of animals used is indicated in parentheses.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045404&req=5

pone-0017117-g006: Potassium-induced relaxation in aortic rings from untreated (CT) and lead-treated (Pb+2) rats previously incubated in a K+-free medium and contracted with phenylephrine before and after incubation with 100 µM ouabain (A).Densitometry analyses of the western blots for the alpha-1 subunit (B) and alpha-2 subunit (C) in aortas from untreated (CT) and lead-treated rats (Pb+2). Representative blots are also shown. *P<0.05 (CT vs. Pb+2) by Student's t-test or two-way ANOVA followed by a Bonferroni test. #P<0.05 (CT OUA vs. Pb+2 OUA) by two-way ANOVA followed by a Bonferroni test. Number of animals used is indicated in parentheses.
Mentions: We hypothesized that an increase in the Na+/K+-ATPase activity might be causing the reduction in vascular reactivity after phenylephrine treatment in the aortas from lead-treated rats. The activity of the sodium pump, which was evaluated by the potassium-induced relaxation curves before 100 µM ouabain incubation, increased in aortic rings from treated rats (Figure 6). Preincubation of intact segments with ouabain (100 µM) for 30 min in K+-free medium induced an increase in vascular tone in the aortas from both groups, but the increase was smaller in the last concentration of segments from lead-treated rats (Figure 6 A). In addition to this finding, the protein expression of the Na+/K+-ATPase alpha-1 subunit increased after lead treatment (Figure 6 B). However, the protein expression of the alpha-2 subunit of Na+/K+-ATPase was similar in the aortas from untreated and lead-treated rats (Figure 6 C).

Bottom Line: Lead treatment had the following effects: increase in systolic blood pressure (SBP); reduction of contractile response to phenylephrine (1 nM-100 µM) of aortic rings; unaffected relaxation induced by acetylcholine (0.1 nM-300 µM) or sodium nitroprusside (0.01 nM-0.3 µM).This effect is accompanied by increased p-eNOS, iNOS protein expression and Na(+)/K(+)-ATPase functional activity.These factors might be a compensatory mechanism to the increase in SBP.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Espírito Santo, Brazil.

ABSTRACT
Chronic lead exposure induces hypertension and alters endothelial function. However, treatment with low lead concentrations was not yet explored. We analyzed the effects of 7 day exposure to low lead concentrations on endothelium-dependent responses. Wistar rats were treated with lead (1st dose 4 µg/100 g, subsequent dose 0.05 µg/100 g, i.m. to cover daily loss) or vehicle; blood levels attained at the end of treatment were 9.98 µg/dL. Lead treatment had the following effects: increase in systolic blood pressure (SBP); reduction of contractile response to phenylephrine (1 nM-100 µM) of aortic rings; unaffected relaxation induced by acetylcholine (0.1 nM-300 µM) or sodium nitroprusside (0.01 nM-0.3 µM). Endothelium removal, N(G)-nitro-L-arginine methyl ester (100 µM) and tetraethylammonium (2 mM) increased the response to phenylephrine in treated rats more than in untreated rats. Aminoguanidine (50 µM) increased but losartan (10 µM) and enalapril (10 µM) reduced the response to phenylephrine in treated rats. Lead treatment also increased aortic Na(+)/K(+)-ATPase functional activity, plasma angiotensin-converting enzyme (ACE) activity, protein expression of the Na(+)/K(+)-ATPase alpha-1 subunit, phosphorylated endothelial nitric oxide synthase (p-eNOS), and inducible nitric oxide synthase (iNOS). Our results suggest that on initial stages of lead exposure, increased SBP is caused by the increase in plasma ACE activity. This effect is accompanied by increased p-eNOS, iNOS protein expression and Na(+)/K(+)-ATPase functional activity. These factors might be a compensatory mechanism to the increase in SBP.

Show MeSH
Related in: MedlinePlus