Abstract
Lead (Pb^2+^) has been implicated in the development of hypertension and atherosclerosis. The proliferation of vascular smooth muscle cells (VSMC) is a central feature of both conditions and there is evidence that Pb^2+^ potentiates serumโdependent cell growth. The aim of this work was to examine the role of phospholipase A~2~ in mitogenโdependent VSMC proliferation and determine if Pb^2+^ interacts with this system in order to potentiate mitotic events. It was observed that cell proliferation induced by angiotensin II, or fetal bovine serum, required the activation of a Ca^2+^โdependent cytosolic phospholipase A~2~ and the subsequent release of unesterified arachidonic acid. This path was affected by Pb^2+^ as the metal increased the amount of arachidonic acid accumulation induced by either mitogen. In addition, Pb^2+^ potentiated mitogenโinduced DNA synthesis when present at lower doses (0.02 or 0.2 mg%), but had no effect on DNA synthesis, or cell numbers, in unstimulated cells. However, a high dose (2 mg%) of Pb^2+^ attenuated the DNA synthesis stimulated by angiotensin II, or serum, but induced the accumulation of unesterified arachidonic acid in unstimulated cells. A biphasic effect of Pb^2+^ on cell numbers and viability was also observed as 0.02 or 0.2 mg% Pb^2+^ did not affect cell numbers or trypan blue exclusion in unstimulated cells, while 2 mg% Pb^2+^ reduced cell numbers and viability. It appeared, therefore, that the lower concentrations of Pb^2+^ increased arachidonic acid release and DNA synthesis only in stimulated VSMC, perhaps due to further activation of a Ca^2+^โdependent processes. In contrast, the high dose of Pb^2+^ reduced DNA synthesis in stimulated cells and reduced cell numbers and viability in unstimulated cells, which may relate to the noted increase in unesterified arachidonic acid. ยฉ 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:245โ253, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10045