The role of cyclooxygenase (COX)-2 derived prostanoids on vasoconstrictor responses to phenylephrine is increased by exposure to low mercury concentration.
We have previously demonstrated that chronic exposure to low-dose of mercury induced endothelial dysfunction and increased vasoconstrictor responses. The aim of this work was to investigate if mercury exposure alters contractile prostanoids production from cyclooxygenase-2 (COX-2) and its contribution to phenylephrine responses. For this, aortic segments from 3-month old Wistar rats daily treated with HgCl(2) (1(st) dose 4.6 microg/kg, subsequent dose 0.07 microg/kg/day, i.m.) or vehicle for 30 days were used. Mercury treatment did not affect systolic blood pressure but increased phenylephrine-induced vasoconstriction. The non selective COX inhibitor, indomethacin (10 micromol/l) reduced the response to phenylephrine more in aortic segments from mercury-treated than control rats. The selective COX-2 inhibitor NS 398 (1 micromol/l), the thromboxane A(2)/prostaglandin H(2) receptor (TP) antagonist SQ 29,548 (1 micromol/l), the TXA(2) synthase inhibitor furegrelate (1 micromol/l), the EP(1) receptor antagonist SC 19220 (1 micromol/l) and the AT(1) receptor antagonist losartan (10 micromol/l) reduced phenylephrine response only in vessels from mercury-treated rats. TXA(2) and PGE(2) levels were greater in the incubation medium of vessels from treated than untreated rats; NS 398 decreased these levels only in the mercury group. COX-2 protein was localized in adventitial and endothelial cells. Aortic COX-2 mRNA expression and plasma angiotensin converting enzyme activity were greater in mercury-treated rats. These results suggest that treatment with low doses of mercury increases the release of COX-2-derived vasoconstrictor prostanoids and its participation in phenylephrine responses. The increased activation of the renin-angiotensin system after mercury treatment might be associated to this increased COX-2 activity.
Departamento de Farmacologia, Universidad Autonoma de Madrid, Madrid, Spain.
F M
FM
Pecanha
G A
GA
Wiggers
A M
AM
Briones
J V
JV
Perez-Giron
M
M
Miguel
A B
AB
Garcia-Redondo
D V
DV
Vassallo
M J
MJ
Alonso
M
M
Salaices
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000502:physiology*; D004357:Drug Synergism; D008297:Male; D008628:Mercury / Q000008:administration & dosage*; D010656:Phenylephrine / Q000494:pharmacology*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D008628:Mercury