Hypertension promotes integrin expression and reactive oxygen species generation by circulating leukocytes

doi:doi:10.1111/j.1523-1755.2005.00223.x

Abstract

Hypertension promotes integrin expression and reactive oxygen species generation by circulating leukocytes.

Background

Compelling evidence has emerged pointing to the role of oxidative stress in the pathogenesis of hypertension (HTN) in experimental animals. Excess production of reactive oxygen species (ROS) in the renal and vascular tissues has been shown to raise arterial pressure via inactivation of nitric oxide and generation of isoprostanes. Accumulation of inflammatory cells in the renal interstitium has been shown to increase ROS generation in the kidneys of hypertensive animals. In addition, considerable evidence has emerged pointing to spontaneous activation of circulating leukocytes in animals and humans with hereditary HTN. This study was designed to explore whether induction of HTN in genetically normal animals can lead to spontaneous activation and ROS production in circulating leukocytes.

Methods

Integrin expression, superoxide, and hydrogen peroxide production were assessed by flow cytometry in the circulating and splenic leukocytes of Sprague-Dawley rats rendered hypertensive by abdominal aorta banding above the renal arteries, and in sham-operated control rats.

Results

The hypertensive animals studied 4 weeks after abdominal aorta banding exhibited a significant increase in superoxide and H₂O₂ production in the circulating granulocyte, and a marked increase in H₂O₂ production in the blood and splenic helper and cytotoxic T-lymphocytes. This was coupled with a significant up-regulation of CD18 and CD11a in splenic helper T-cells and cytotoxic T cells, and of CD18 in the circulating helper T cells.

Conclusion

Induction of HTN in genetically normotensive rats causes a spontaneous increase in ROS generation in the circulating and splenic leukocytes. This phenomenon can contribute to systemic oxidative stress, inflammation, cardiovascular and renal complications in hypertensive animals.

Keywords:

oxidative stress, inflammation, hypertension, leukocytes, atherosclerosis, integrin expression, cardiovascular disease, aortic coarctation

Vascular Biology – Hemodynamics – Hypertension