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Air Quality Criteria for Lead Volume II of II - (NEPIS)(EPA) - US ...

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AX5-66<br />

Reference<br />

Watts et al.<br />

(1995)<br />

Rodríguez-<br />

Iturbe et al.<br />

(2005)<br />

Table AX5-5.2. Studies <strong>of</strong> the Effects <strong>of</strong> <strong>Lead</strong> Exposure on PKC Activity, NFkB Activation, and Apoptosis<br />

Species/<br />

Tissue<br />

Isolated rabbit<br />

mesenteric<br />

artery<br />

Pb Exposure Measured Parameters<br />

Age/<br />

Weight n Dosage Duration Pb Level CVS Other Interventions Results<br />

N/A 5–6 sets per<br />

experiment<br />

Male SD rats 200 g 8 Pb group<br />

9 controls<br />

Pb acetate<br />

10 −10 −10 −3 M<br />

Pb acetate<br />

100 ppm in<br />

drinking<br />

water<br />

Immediate<br />

(contraction)<br />

5 −10 −10 −3 M<br />

medium<br />

Vascular<br />

contraction<br />

3 mo N/A NFkB activation,<br />

apoptosis, Ang <strong>II</strong><br />

positive cells,<br />

macrophage/T cell<br />

infiltration and<br />

nitrotyrosine staining<br />

in renal tissue<br />

Preincubation<br />

w/PKC<br />

activators, PKC<br />

inhibitor or<br />

verapamil <strong>for</strong><br />

30–60 min +<br />

endothelium<br />

denudation<br />

Pb acetate induced<br />

contraction which was<br />

potentiated by PKC<br />

activators and<br />

attenuated by PKC<br />

inhibitor (role <strong>of</strong><br />

PKC). CCB<br />

attenuated Pb-induced<br />

contraction<br />

(contribution <strong>of</strong> Ca 2+<br />

entry). Removal <strong>of</strong><br />

endothelium did not<br />

affect Pb-induced<br />

vasoconstriction.<br />

Pb-exposed animals<br />

showed<br />

tubuloniterstitial<br />

accumulation <strong>of</strong><br />

activated T-cells,<br />

macrophages and Ang<br />

<strong>II</strong> positive cells, NFkB<br />

activation increased<br />

apoptosis and<br />

nitrotyrosine staining<br />

in the kidney.

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