Lead, hypertension, and the renin-angiotensin system in rats

Rats were exposed continuously to Pb in utero and after birth by giving their mothers, during pregnancy and lactation, drinking water containing 0, 100, or 500 ppm Pb (as Pb acetate) and then continuing this regimen after weaning. Male rats received 100 ppm developed a significant elevation of systolic blood pressure (152 +/- 3.7 mm Hg vs. 135 +/- 5.6 for controls) at 3 1/2 months and remained hypertensive until sacrifice at 6 months; 500 ppm rats remained normotensive. Both 100 ppm and 500 ppm females remained normotensive. At 6 months, PRA was significantly reduced in the 100 ppm male group but was normal in the 500 ppm group. There were dose-dependent decreases in the AII/PRA ration and in renal renin. Pulmonary converting enzyme activity was not changed by Pb exposure. Blood [Pb] was 40 and 71 mug/dl, respectively, and kidney [Pb] was 4.8 and 22.9 mug/gm. Renal histology was normal in the 100 ppm group. We conclude that doses of Pb which produce blood [Pb] seen in many people are capable of inducing modest hypertension in male rats; higher doses fail to do so. The hypertension is associated with a reduction in PRA and All and therefore is unlikely to be due to hyperactivity of the RAS. (J Lab Clin Med 99:354, 1982.)