Endothelial nitric oxide synthase and cyclooxygenase are activated by hydrogen peroxide in renal hypertensive rat aorta

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In this work, we hypothesized that cyclooxygenase (COX) activity can be regulated by nitric oxide (NO) and hydrogen peroxide (H2O2). In the renal hypertension (2K-1C), phenylephrine (PE)-induced contraction was lower than in normotensive (2K) rat aortas. This impaired contraction is due to NO/H2O2- induced vasodilation. We evaluated the effects of H2O2 on the activity of COX and endothelial NO-Synthase (eNOS) in 2K-1C rat aortas stimulated with PE. Responses for PE or H2O2 were evaluated in 2K-1C and 2K rat aortas, without or with inhibitors for COX (Indomethacin) or eNOS (L-NAME). COX isoforms expression was evaluated by Western blotting. eNOS inhibition was tested on thromboxane A2 (TXA2) and prostacyclin (PGI2) production. PE-induced contraction was lower in 2K-1C than in 2K. Indomethacin reduced PE-induced contraction in 2K, but it had no effect in 2K-1C. L-NAME reversed indomethacin-induced effect in 2K and it normalized PE-induced contraction in 2K-1C to the normotensive levels. COX-1 and COX-2 expression, TXA2 and PGI2 production were higher in 2K-1C than in 2K. eNOS inhibition did no modify TXA2/PGI2 production. In low concentrations, H2O2 induced relaxation only in 2K that was abolished by L-NAME while the contractions induced by high concentrations were abolished by indomethacin in both 2K and 2K-1C. The activity/expression of COX, and TXA2/PGI2 production were increased in 2K-1C, which were not modified by eNOS. High levels of H2O2 increased the endothelial COX activity, which induced contraction. Therefore, an high increase in H2O2 production may increase COX-induced vasoconstriction rather than eNOS-induced relaxation, which might contribute to aggravate hypertension.

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