Low nanomolar concentration of mercury chloride increases vascular reactivity to phenylephrine and local angiotensin production in rats.
Exposure to mercury at nanomolar level affects cardiac function but its effects on vascular reactivity have yet to be investigated. Pressor responses to phenylephrine (PHE) were investigated in perfused rat tail arteries before and after treatment with 6 nM HgCl2 during 1 h, in the presence (E+) and absence (E-) of endothelium, after L-NAME (10(-4) M), indomethacin (10(-5 )M), enalaprilate (1 microM), tempol (1 microM) and deferoxamine (300 microM) treatments. HgCl2 increased sensitivity (pD2) without modifying the maximum response (Emax) to PHE, but the pD2 increase was abolished after endothelial damage. L-NAME treatment increased pD2 and Emax. However, in the presence of HgCl2, this increase was smaller, and it did not modify Emax. After indomethacin treatment, the increase of pD2 induced by HgCl2 was maintained. Enalaprilate, tempol and deferoxamine reversed the increase of pD2 evoked by HgCl2. HgCl2 increased the angiotensin converting enzyme (ACE) activity explaining the result obtained with enalaprilate. Results suggest that at nanomolar concentrations HgCl2 increase the vascular reactivity to PHE. This response is endothelium mediated and involves the reduction of NO bioavailability and the action of reactive oxygen species. The local ACE participates in mercury actions and depends on the angiotensin II generation.
Wiggers
Giulia Alessandra
GA
Department of Physiological Sciences, Federal University of Espírito Santo, Brazil. giuliawp@yahoo.com
Stefanon
Ivanita
I
Padilha
Alessandra Simão
AS
Peçanha
Franck Maciel
FM
Vassallo
Dalton Valentim
DV
Oliveira
Edilamar Menezes
EM
D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D015773:Enalaprilat / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013623:Tail / Q000098:blood supply; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D000809:Angiotensins; D004338:Drug Combinations; D014874:Water Pollutants, Chemical; D010656:Phenylephrine; D008627:Mercuric Chloride; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat; D019331:NG-Nitroarginine Methyl Ester