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(Hypertension. 2003;41:715.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Heme Oxygenase Attenuates Angiotensin II-Mediated Increase in Cyclooxygenase-2 Activity in Human Femoral Endothelial Cells

Giovanni Li Volti; Francesca Seta; Michal L. Schwartzman; Alberto Nasjletti; Nader G. Abraham

From the Departments of Medicine and Pharmacology, New York Medical College (G.L.V., F.S., M.L.S., A.N., N.G.A.), Valhalla; and The Rockefeller University (N.G.A.), New York, NY.

Correspondence to Dr Nader G. Abraham, Professor of Pharmacology, New York Medical College, Valhalla, NY 10595. E-mail nader_abraham{at}nymc.edu

Heme oxygenase (HO) regulates cellular heme levels and catalyzes the formation of bilirubin and carbon monoxide. We hypothesize that the status of the endothelial HO system influences the angiotensin (Ang) II-induced increase in the endothelial production of prostaglandin I₂ (PGI₂) (measured as 6-keto-PGF₁) and prostaglandin E₂ (PGE₂), eicosanoids that modulate the vascular actions of Ang II. In the present study, we determined the effect of interventions that suppress HO activity or induce HO-1 gene expression on Ang II-mediated increase in 6-keto-PGF₁and PGE₂ in cultures of human femoral artery endothelial cells. Incubation of endothelial cells with Ang II (100 ng/mL) for 24 hours increased the levels of both 6-keto-PGF₁ and PGE₂ in the culture media. This effect of Ang II on prostaglandin production by endothelial cells was attenuated in cells treated with SnCl₂ (10 µmol/L), an inducer of HO-1, but was magnified in cells treated with the HO inhibitor ZnDPP or heme. Upregulation of HO-1 gene expression by retrovirus-mediated delivery of the human HO-1 gene also attenuated heme and Ang II-induced prostaglandin synthesis. Of note, prostaglandin synthesis by lysates of endothelial cells stimulated with heme or Ang II appear to involve COX-2, because it was blunted by NS-398, which is presumed to inhibit COX-2 specifically. These results indicate that overexpression of the HO system exerts an inhibitory influence on Ang II-induced synthesis of prostaglandins by endothelial cells.

Key Words: heme oxygenase • cyclooxygenase activity • prostaglandins • angiotensin II • endothelial cell • gene transfer

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