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

The effects of endothelium removal (E−) (A, B) and NG-nitro-L-arginine methyl ester (L-NAME, 100 µM) (D, E) on the concentration-response curve for phenylephrine treatment in aortic rings from untreated (CT) and lead-treated rats (Pb+2).The inset shows differences in area under the concentration-response curves (dAUC) in endothelium–denuded and intact segments (C) and in the presence and absence of L-NAME (F). Densitometry analyses of western blots for endothelial nitric oxide synthase (eNOS) and phosphorylated endothelial nitric oxide synthase (p-eNOS) protein expression in aortas from untreated (CT) and lead-treated rats (Pb+2) (G). Representative blots are also shown. *P<0.05 by Student's t-test. Number of animals used is indicated in parentheses.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3045404&req=5

pone-0017117-g002: The effects of endothelium removal (E−) (A, B) and NG-nitro-L-arginine methyl ester (L-NAME, 100 µM) (D, E) on the concentration-response curve for phenylephrine treatment in aortic rings from untreated (CT) and lead-treated rats (Pb+2).The inset shows differences in area under the concentration-response curves (dAUC) in endothelium–denuded and intact segments (C) and in the presence and absence of L-NAME (F). Densitometry analyses of western blots for endothelial nitric oxide synthase (eNOS) and phosphorylated endothelial nitric oxide synthase (p-eNOS) protein expression in aortas from untreated (CT) and lead-treated rats (Pb+2) (G). Representative blots are also shown. *P<0.05 by Student's t-test. Number of animals used is indicated in parentheses.

Mentions: Results are expressed as mean ± SEM of the number of animals shown in Fig. 2; Rmax, maximal effect (expressed as a percentage of the maximal response induced by 75 mM KCl); pD2, −log one-half Rmax; Control; E−, endothelium removal; L-NAME, NG-nitro-L-arginine methyl ester; indomethacin. P<0.05 vs. untreated control rats (#) and lead-treated control rats (*).


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)

The effects of endothelium removal (E−) (A, B) and NG-nitro-L-arginine methyl ester (L-NAME, 100 µM) (D, E) on the concentration-response curve for phenylephrine treatment in aortic rings from untreated (CT) and lead-treated rats (Pb+2).The inset shows differences in area under the concentration-response curves (dAUC) in endothelium–denuded and intact segments (C) and in the presence and absence of L-NAME (F). Densitometry analyses of western blots for endothelial nitric oxide synthase (eNOS) and phosphorylated endothelial nitric oxide synthase (p-eNOS) protein expression in aortas from untreated (CT) and lead-treated rats (Pb+2) (G). Representative blots are also shown. *P<0.05 by Student's t-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-g002: The effects of endothelium removal (E−) (A, B) and NG-nitro-L-arginine methyl ester (L-NAME, 100 µM) (D, E) on the concentration-response curve for phenylephrine treatment in aortic rings from untreated (CT) and lead-treated rats (Pb+2).The inset shows differences in area under the concentration-response curves (dAUC) in endothelium–denuded and intact segments (C) and in the presence and absence of L-NAME (F). Densitometry analyses of western blots for endothelial nitric oxide synthase (eNOS) and phosphorylated endothelial nitric oxide synthase (p-eNOS) protein expression in aortas from untreated (CT) and lead-treated rats (Pb+2) (G). Representative blots are also shown. *P<0.05 by Student's t-test. Number of animals used is indicated in parentheses.
Mentions: Results are expressed as mean ± SEM of the number of animals shown in Fig. 2; Rmax, maximal effect (expressed as a percentage of the maximal response induced by 75 mM KCl); pD2, −log one-half Rmax; Control; E−, endothelium removal; L-NAME, NG-nitro-L-arginine methyl ester; indomethacin. P<0.05 vs. untreated control rats (#) and lead-treated control rats (*).

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