title: Persistence of EDHF pathway and impairment of the nitric oxide pathway after chronic mercury chloride exposure in rats: mechanisms of endothelial dysfunction.
abstract: Chronic mercury exposure impairs vascular function, leading to the depression of endothelium-dependent vasodilatation. Loss of the nitric oxide (NO) pathway has been implicated, but little is known about effects on other endothelial mediators. This study investigated the mechanisms of endothelial dysfunction in rats subjected to chronic mercury chloride exposure. The endothelium-dependent relaxation of rat aorta evoked by acetylcholine (ACh) and isoproterenol was impaired in a dose-dependent manner by chronic mercury chloride exposure. Endothelium-independent responses to sodium nitroprusside (SNP) were not affected by chronic mercury chloride exposure. In healthy vessels, ACh-induced relaxation was inhibited by L-N-nitroarginine methyl ester (L-NAME; 10(-4)                M) and partially by glybenclamide (10(-5)                M), indicating the involvement of NO and endothelium-derived hyperpolarizing factor (EDHF). In vessels from mercury-exposed rats, responses to ACh were insensitive to L-NAME but were significantly reduced by glybenclamide, indicating selective loss of NO-mediated relaxation. In vessels from mercury-exposed rats, responses to ACh were partially restored after treatment with the antioxidant, superoxide dismutase (SOD) and catalase, this effect was not seen when aorta from exposed group was incubated with L-NAME along with SOD and catalase indicating selective loss of NO-mediated vasodilatation and with no affect the EDHF-mediated component of relaxation. The results imply that chronic mercury exposure selectively impairs the NO pathway as a consequence of oxidative stress, while EDHF is able to maintain endothelium-dependent relaxation at a reduced level.
authors.affiliation: Indian Council of Medical Research ICMR, New Delhi, India. swatiomanwar@gmail.com
authors.forename: S
authors.initials: S
authors.lastname: Omanwar
authors.forename: K
authors.initials: K
authors.lastname: Ravi
authors.forename: M
authors.initials: M
authors.lastname: Fahim
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D001685:Biological Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008627:Mercuric Chloride / Q000493:pharmacokinetics / Q000633:toxicity*; D008628:Mercury / Q000097:blood; D009130:Muscle, Smooth / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014652:Vascular Diseases / Q000378:metabolism / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D004785:Environmental Pollutants; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009599:Nitroprusside; D009569:Nitric Oxide; D008315:Malondialdehyde; D008627:Mercuric Chloride; D008628:Mercury; D007545:Isoproterenol; D000109:Acetylcholine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester