Open AccessChronic Lead Exposure May Inhibit Endothelium-Dependent Hyperpolarizing Factor in Rats
Author(s) -
Hirotaka Oishi,
Mitsuyoshi Nakashima,
Tadahide Totoki,
Katsumaro Tomokuni
Publication year - 1996
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-199610000-00013
Subject(s) - phenylephrine , endothelium , acetylcholine , hyperpolarization (physics) , endothelium derived hyperpolarizing factor , endocrinology , medicine , endothelium derived relaxing factor , mesenteric arteries , aorta , chemistry , contraction (grammar) , isometric exercise , blood vessel , nitric oxide , artery , blood pressure , charybdotoxin , nuclear magnetic resonance spectroscopy , organic chemistry
We designed experiments to determine the effect of chronic lead exposure on endothelium-dependent responses to acetylcholine (Ach) in rat isolated blood vessels. Male Wistar rats were maintained for 1 or 3 months with or without oral lead administration. Membrane potential and isometric tension were measured in mesenteric arteries. Ach caused concentration- and endothelium-dependent relaxation in rings with endothelium contracted with phenylephrine (PE). There was no significant difference in relaxation between lead-exposed and control animals. In the presence of NG-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 significantly 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 regardless of duration. These data indicate that both endothelium-dependent hyperpolarization 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).