Chronic lead exposure may inhibit endothelium-dependent hyperpolarizing factor in rats.
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).
Department of Community Health Science, Saga Medical School, Japan.
H
H
Oishi
M
M
Nakashima
T
T
Totoki
K
K
Tomokuni
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic; D001685:Biological Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D007854:Lead / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D007854:Lead; D009569:Nitric Oxide; D006152:Cyclic GMP; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester