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

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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.

Journal of Physiology and Pharmacology

2010

tom 61

nr 1

29-36

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.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology

1 Alonso M. J.

1 Briones A. M.

1 Garcia-Redondo A. B.

1 Miguel M.

1 Pecanha F. M.

1 Perez-Giron J. V.

1 Salaices M.

1 Vassallo D. V.

1 Wiggers G. A.

1 2010

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