The role of cyclooxygenase [COX]-2 derived prostanoids on vasoconstrictor responses to phenylephrine is increased by exposure to low mercury concentration

• Autorzy: Pecanha F. M. , Wiggers G.A. , Briones A.M. , Perez-Giron J.V. , Miguel M. , Garcia-Redondo A.B. , Vassallo D.V. , Alonso M.J. , Salaices M.
• Języki publikacji: EN

Abstrakty

EN

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 HgCl2 (1st dose 4.6 µg/kg, subsequent dose 0.07 µg/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 µmol/l) reduced the response to phenylephrine more in aortic segments from mercury-treated than control rats. The selective COX-2 inhibitor NS 398 (1 µmol/l), the thromboxane A2/prostaglandin H2 receptor (TP) antagonist SQ 29,548 (1 µmol/l), the TXA2 synthase inhibitor furegrelate (1 µmol/l), the EP1 receptor antagonist SC 19220 (1 µmol/l) and the AT1 receptor antagonist losartan (10 µmol/l) reduced phenylephrine response only in vessels from mercury-treated rats. TXA2 and PGE2 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.

Słowa kluczowe

EN

cyclooxygenase-2; prostanoid; vasoconstrictor response; phenylephrine; exposure; mercury concentration; endothelial dysfunction; angiotensin II; angiotensin converting enzyme; thromboxane A2

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2010
• Tom: 61
• Numer: 1
• Opis fizyczny: p.29-36,fig.,ref.

Twórcy

autor

Pecanha F. M.

• Universidad Autonoma de Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain

autor

Wiggers G.A.

autor

Briones A.M.

autor

Perez-Giron J.V.

autor

Miguel M.

autor

Garcia-Redondo A.B.

autor

Vassallo D.V.

autor

Alonso M.J.

autor

Salaices M.

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