EFFECT OF CHRONIC LEAD-EXPOSURE ON THE DIRECT AND INDIRECT COMPONENTS OF THE CARDIAC RESPONSE TO NOREPINEPHRINE

Lead exposure to neonates produces an enhanced sensitivity of the adult rat heart to the arrhythmogenic effect of norepinephrine. The present study examines the possibility that both the direct and reflex effects of norepinephrine might be affected by early lead exposure. Rats were exposed to 0.2% lead acetate via maternal milk from birth to weaning, then were allowed a lead-free period of 3 months. Rat pups of sodium acetate-treated dams served as controls. Norepinephrine produced more ventricular extrasystoles in lead-exposed rats than methoxamine at doses that produced similar changes in mean systemic blood pressure. While bilateral vagotomy or atropine pretreatment decreased the frequency of cardiac arrhythmias, norepinephrine still caused significantly more extrasystoles in lead-exposed than control rats. The arrhythmogenic effect of methoxamine observed in lead-exposed animals could be completely prevented by bilateral vagotomy. Isolated perfused hearts from lead-exposed animals exhibited more irregularities in rhythm after norepinephrine than hearts from control animals. It is concluded that while effects on the vagus nerve participate in the lead-induced sensitivity to norepinephrine, direct cardiac effects are also involved. © 1979.