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Antioxid Redox Signal. 2015 Aug 1;23(4):295-306. doi: 10.1089/ars.2013.5481. Epub 2014 Feb 6.

Cross-talk Between Nitrate-Nitrite-NO and NO Synthase Pathways in Control of Vascular NO Homeostasis.

Author information

1
1 Department of Physiology and Pharmacology, Karolinska Institutet , Stockholm, Sweden .
2
2 Department of Medical Cell Biology, Uppsala University , Uppsala, Sweden .
3
3 Division of Anesthesiology and Intensive Care, Department of Physiology and Pharmacology, Karolinska Institutet , Stockholm, Sweden .

Abstract

AIMS:

Inorganic nitrate and nitrite from endogenous and dietary sources have emerged as alternative substrates for nitric oxide (NO) formation in addition to the classic L-arginine NO synthase (NOS)-dependent pathway. Here, we investigated a potential cross-talk between these two pathways in the regulation of vascular function.

RESULTS:

Long-term dietary supplementation with sodium nitrate (0.1 and 1 mmol kg(-1) day(-1)) in rats caused a reversible dose-dependent reduction in phosphorylated endothelial NOS (eNOS) (Ser1177) in aorta and a concomitant increase in phosphorylation at Thr495. Moreover, eNOS-dependent vascular responses were attenuated in vessels harvested from nitrate-treated mice or when nitrite was acutely added to control vessels. The citrulline-to-arginine ratio in plasma, as a measure of eNOS activity, was reduced in nitrate-treated rodents. Telemetry measurements revealed that a low dietary nitrate dose reduced blood pressure, whereas a higher dose was associated with a paradoxical elevation. Finally, plasma cyclic guanosine monophosphate increased in mice that were treated with a low dietary nitrate dose and decreased with a higher dose.

INNOVATION AND CONCLUSIONS:

These results demonstrate the existence of a cross-talk between the nitrate-nitrite-NO pathway and the NOS-dependent pathway in control of vascular NO homeostasis.

PMID:
24224525
PMCID:
PMC4523008
DOI:
10.1089/ars.2013.5481
[Indexed for MEDLINE]
Free PMC Article

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