CHRONIC LEAD-EXPOSURE MAY INHIBIT ENDOTHELIUM-DEPENDENT HYPERPOLARIZING FACTOR IN RATS

We designed experiments to determine the effect of chronic lead exposu re on endothelium-dependent responses to acetylcholine (Ach) in rat is olated blood vessels. Male Wistar rats were maintained for 1 or 3 mont hs with or without oral lead administration. Membrane potential and is ometric tension were measured in mesenteric arteries. Ach caused conce ntration- and endothelium-dependent relaxation in rings with endotheli um contracted with phenylephrine (PE). There was no significant differ ence in relaxation between lead-exposed and control animals. In the pr esence of N-G-nitro-L-arginine methyl ester (L-NAME), both endothelium -dependent hyperpolarization and relaxation to Ach were significantly reduced in animals from the 3-month lead-exposed group. In aorta from lead exposed groups, endothelium-dependent relaxation to Ach was not s ignificantly different from that of age-matched controls, whereas both were completely inhibited in the presence of L-NAME. The basal levels of cyclic GMP in the aorta were not affected by lead exposure regardl ess of duration. These data indicate that both endothelium-dependent h yperpolarization and L-NAME-resistant relaxation decrease with chronic lead exposure in rat mesenteric arteries and suggest that lead is an inhibitor or endothelium-derived hyperpolarizing factor (EDHF).