Catcholamine and nitric oxide systems as targets of chronic lead exposure in inducing selective functional impairment

Rats were exposed for ten months to 60 ppm of lead (Pb, as acetate) in drin king water to further assess cardiovascular effects of chronic Pb exposure. At the end of the treatment, mean blood Pb was 3.1+/-0.3 mug/dL in the con trol rats and 22.8+/-1.2 mug/dL in the Pb-exposed rats (means+/-SE, n=12 in each group); these values were not comparable to those of humans. Pb great ly increased plasma levels of noradrenaline (NA) and adrenaline (A), but no t those of L-DOPA and dopamine; monoaminoxidase activity was augmented by P b, mostly in the aorta and in the liver; the aorta, liver, heart and kidney showed discrete histopathological alterations in the Pb-exposed fats, in w hich plasma levels of nitric oxide (NO, determined as L-citrulline) were re duced. Pb was able to induce blood hypertension, resulting from increase of cardiac inotropism and, mostly, total peripheral resistance. These data we re discussed also in relation to those obtained in our previous studies car ried out in rats exposed to Pb in drinking water (15-60 ppm) for periods ra nging from five to eighteen months. Pb appeared to increase both sympatheti c nerve activity by central mechanisms (thus increasing plasma NA and A) an d cyclic adenosine monophosphate (cAMP)-dependent availability of calcium i ons (Ca++) for contractile mechanisms in the vascular and cardiac myocells (also through an increased vascular alpha (2)- and myocardial beta (1)-adre noreceptor reactivity). The reduction of plasma NO, contributing to increas e vascular resistance and cardiac inotropism, was explained as a result of actions of Pb on enzyme activities concerned with the kallikrein-kinin (KK) and renin-angiotensin-aldosterone (RAA) systems. It was concluded that chr onic Pb exposure is able to affect selective neuroendocrine (i,e., catechol amine), autacoidal (i.e., KK and RAA) and transductional pathways (i.e., cA MP, NO, Ca++) involved in the cardiovascular function. (C) 2000 Elsevier Sc ience Inc. All rights reserved.