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