title: Involvement of cholinoceptors in cadmium-induced endothelial dysfunction.
abstract: Cadmium (Cd) toxicity was produced in male rats to study the role of cholinoceptors in Cd-induced endothelial dysfunction. The changes in the tension of the aortic rings to constrictor and dilator agonists were compared with those of controls. A Cd-induced significant increase in phenylephrine response was associated with a decrease in basal dilator prostanoid release. In Cd-exposed rings, despite an obvious depression in the acetylcholine (ACh) response, the receptor-independent dilation to the calcium ionophore A23187, which elicits a receptor-independent endothelial relaxation, was slightly elevated (p<0.01), but the smooth muscle cell response to the NO donor, sodium nitroprusside (SNP) remained unaltered. Cadmium decreased both the maximal response to ACh (10(-5) M) and its pirenzepine (Prz) sensitive component. The M1 type cholinoceptor-mediated response to ACh decreased in Cd-exposed rings to 10.30 +/- 5.00% from 38.40 +/- 6.90% (p<0.001). Cadmium also reduced the share of indomethacin 1.64% to 13.92 +/- 2.89% (p<0.01), which correlated well with the changes in the M1-mediated response (r=0.991, p<0.0001). Most of the deleterious effect of Cd appears to be restricted to the M1-dependent ACh response. These findings suggest that Cd produces an endothelial dysfunction by impairing the M1 type cholinoceptor mediated response, which seems to be involved in prostanoid release.
authors.affiliation: Akdeniz University, Medical Faculty, Department of Physiology, 07070 Antalya, Turkey.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Bilgen
authors.forename: Gülsen
authors.initials: G
authors.lastname: Oner
authors.forename: Mustafa
authors.initials: M
authors.lastname: Edremitlioğlu
authors.forename: Zeliha
authors.initials: Z
authors.lastname: Alkan
authors.forename: Selma
authors.initials: S
authors.lastname: Cirrik
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D001013:Aorta, Thoracic; D001285:Atropine / Q000008:administration & dosage / Q000493:pharmacokinetics; D002104:Cadmium / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D000001:Calcimycin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005703:Gallamine Triethiodide / Q000008:administration & dosage / Q000493:pharmacokinetics; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000150:complications; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics; D007672:Kidney Cortex / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000150:complications; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000493:pharmacokinetics; D009599:Nitroprusside / Q000008:administration & dosage / Q000493:pharmacokinetics; D016491:Peripheral Vascular Diseases / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology; D010656:Phenylephrine / Q000008:administration & dosage / Q000493:pharmacokinetics; D010890:Pirenzepine / Q000008:administration & dosage / Q000493:pharmacokinetics; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000187:drug effects* / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D011453:Prostaglandins; D043643:Receptor, Muscarinic M1; D002104:Cadmium; D009599:Nitroprusside; D010656:Phenylephrine; D000001:Calcimycin; D010890:Pirenzepine; D001285:Atropine; D000109:Acetylcholine; D005703:Gallamine Triethiodide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin