Alba, Gonzalo , El Bekay, Rajaa , CHACON FERNANDEZ, PEDRO JOSE, Reyes, M. Edith , Ramos, Eladio , Olivan, Josefina , Jimenez, Juan , Lopez, Jose M. , Martin-Nieto, Jose , Pintado, Elizabeth , Sobrino, Francisco
No
J. Leukoc. Biol.
Article
Científica
4.605
2.647
01/08/2008
000258091600110
Angiotensin II (Ang II) is a peptide hormone able to elicit a strong production of reactive oxygen species by human neutrophils. In this work, we have addressed whether expression of heme oxygenase-1 (HO-1), an antioxidant enzyme, becomes altered in these cells upon Ang II treatment or under hypertension conditions. In neutrophils from healthy and hypertensive subjects, induction of HO-1 mRNA and protein expression with a parallel increase in enzyme activity took place upon treatment with 15-deoxy-Delta(12,14)- PGJ(2) (15dPGJ(2)). However, Ang II prevented HO-1 synthesis by normal neutrophils in vitro, and HO-1 expression was depressed in neutrophils from hypertensive patients in comparison with cells from healthy subjects. In addition, Ang II treatment led to a reduced HO-1 enzyme activity to levels similar to those found in neutrophils from hypertensive patients. NO donors reversed the inhibition of 15dPGJ(2)- dependent HO-1 expression in neutrophils from hypertensive patients, and conversely, inhibition of inducible NO synthase (NOS2) activity counteracted the stimulatory effect of 15dPGJ(2) on HO-1 expression in normal human neutrophils. Moreover, Ang II canceled 15dPGJ(2)-dependent induction of NOS2 mRNA synthesis. Present findings indicate that down-regulation of HO-1 expression in neutrophils from hypertensive subjects is likely exerted through the inhibition of NOS2 expression. Additionally, they underscore the potential usefulness of NO donors as new, therapeutic agents against hypertension.
antioxidant enzymes; polymorphonuclear cells; oxidative stress; nitric oxide