Augmented nitric oxide generation in neutrophils: oxidative and pro-inflammatory implications in hypertension.
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 approximately 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 [Ca(2+)](i) levels. Levels of TNF-alpha and IFN-gamma were comparable, but IL-1beta and CRP levels in SHR plasma were (p<0.05) elevated. This study evidenced significantly enhanced expression of IL-1beta in SHR neutrophils whereas those of TNF-alpha and IFN-gamma 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.
Chatterjee
Madhumita
M
Cardiovascular Pharmacology Unit, Central Drug Research Institute, Lucknow, India.
Saluja
Rohit
R
Tewari
Shikha
S
Barthwal
Manoj Kumar
MK
Goel
Sudhir Kumar
SK
Dikshit
Madhu
M
D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D010586:Phagocytes; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D016207:Cytokines; D016877:Oxidants; D009569:Nitric Oxide; D002097:C-Reactive Protein; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D002118:Calcium