Multiple short-term effects of lead on the renin-angiotensin system

We previously demonstrated that lead (3 mg/kg iv) sharply raises PRA in dogs. In the present study, the short-term effects of the same dose of lead on renin secretion, hepatic removal of renin, and arterial AII levels were measured in anesthetized dogs. Despite large increases in PRA in all nine lead-treated dogs, renin secretion increased in only three out of nine lead-treated animals (those with the lowest baseline renin secretion). Hepatic extraction of renin was eliminated by lead, and so total hepatic removal of renin became zero by 2 or 3 hr after lead administration. Finally, despite large increases in PRA, AII levels did not rise after lead. The linear relationship of AII to PRA seen in animals not treated with lead was changed, so that after lead, AII levels were disproportionately low for the corresponding level of PRA. It is concluded that lead may increase renin secretion in animals otherwise unstimulated to secrete but that the major mechanism for the short-term rise in PRA after lead is elimination of hepatic removal of renin; further, lead prevents AII from rising proportionately with PRA, presumably by inhibiting angiotensin-converting enzyme.