Augmented nitric oxide generation in neutrophils: Oxidative and pro-inflammatory implications in hypertension

Abstract

The present study explores expression of NOS and pro-inflammatory cytokines, NOS catalysis and NO mediated modulation of oxidative response and apoptosis in neutrophils from spontaneously hypertensive rats (SHR). Neutrophils from SHR showed ∼3-fold increments in iNOS expression, 1.5-fold increments in nOS expression and calcium independent NOS catalysis, whereas GTPCH expression was unaltered. Although phagocytic potential was comparable, neutrophils from SHR demonstrated augmented oxidative burst, which was reduced by NOS inhibition or in the presence of NO scavenger. SHR neutrophils also exhibited enhanced MPO catalysis and [Ca²⁺]_i levels. Levels of TNF-α and IFN-γ were comparable, but IL-1β and CRP levels in SHR plasma were (p<0.05) elevated. This study evidenced significantly enhanced expression of IL-1β in SHR neutrophils whereas those of TNF-α and IFN-γ were unaltered. Moreover neutrophils from SHR exhibited (p<0.01) delayed apoptotic response and sustained NO generation, as evident from elevated nitrite levels in neutrophil culture supernatant above the control levels. Results obtained indicate an augmented NO generation from neutrophils during hypertension which might fortify their attribute to the oxidative and inflammatory stress in SHR, emphasizing the importance of neutrophils in hypertension.

Keywords::

• Neutrophil
• nitric oxide synthase
• hypertension
• phagocytosis
• oxidative burst
• cytokines
• apoptosis

Acknowledgeement

We acknowledge the excellent technical assistance of Mr. A.L. Vishwakarma and Ms.M. Chaturvedi for the flow cytometric studies. The Senior Research Fellowship from the Council of Scientific and Industrial Research, New Delhi, India to RS and Indian Council of Medical Research, New Delhi, India to MC is acknowledged. This study was supported by a financial grant to MD from the Department of Biotechnology, New Delhi, India.

Declaration of interest: The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.

This paper was first published online on Early Online on 21 September 2009.