Nitrate-nitrite-NO pathway in health and disease
Our research group studies the biological chemistry, physiological and therapeutic roles of nitric oxide (NO) and chemically related compounds.
We focus on exploring the role of the nitrate-nitrite-NO pathway for the generation of nitric oxide (NO) and other reactive nitrogen intermediates in mammals.
The inorganic anions nitrate (NO³¯) and nitrite (NO²¯) can recycle in vivo to form NO and other bioactive nitrogen oxides. This represents an important alternative source of NO, especially during hypoxia/ischemia when the classical L-arginine/NO synthase pathway may be dysfunctional. A picture is now emerging suggesting important biological functions of the nitrate-nitrite-NO pathway with provocative implications in relation to the diet and cardiovascular homeostasis. In addition, an expanding number of studies suggest a therapeutic potential for nitrate and nitrite in cardiovascular and metabolic diseases.
In a translational approach our research spans from experimental in vitro studies to human clinical trials.
- Swedish Research Council (VR)
- Swedish Heart and Lung Foundation
- Stockholm County Council (ALF)
- Jochnick Foundation
AMP-activated protein kinase activation and NADPH oxidase inhibition by inorganic nitrate and nitrite prevent liver steatosis.
Cordero-Herrera I, Kozyra M, Zhuge Z, McCann Haworth S, Moretti C, Peleli M, et al
Proc. Natl. Acad. Sci. U.S.A. 2019 01;116(1):217-226
Metabolic Effects of Dietary Nitrate in Health and Disease.
Lundberg JO, Carlström M, Weitzberg E
Cell Metab. 2018 Jul;28(1):9-22
Organ uptake and release of inorganic nitrate and nitrite in the pig.
Eriksson KE, Yang T, Carlström M, Weitzberg E
Nitric Oxide 2018 05;75():16-26
Dietary nitrate improves age-related hypertension and metabolic abnormalities in rats via modulation of angiotensin II receptor signaling and inhibition of superoxide generation.
Hezel M, Peleli M, Liu M, Zollbrecht C, Jensen BL, Checa A, et al
Free Radic. Biol. Med. 2016 10;99():87-98
Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases.
Omar SA, Webb AJ, Lundberg JO, Weitzberg E
J. Intern. Med. 2016 Apr;279(4):315-36
Strategies to increase nitric oxide signalling in cardiovascular disease.
Lundberg JO, Gladwin MT, Weitzberg E
Nat Rev Drug Discov 2015 Sep;14(9):623-41
Effects of long-term dietary nitrate supplementation in mice.
Hezel MP, Liu M, Schiffer TA, Larsen FJ, Checa A, Wheelock CE, et al
Redox Biol 2015 Aug;5():234-242
Effects of hyperbaric oxygen on nitric oxide generation in humans.
Uusijärvi J, Eriksson K, Larsson AC, Nihlén C, Schiffer T, Lindholm P, et al
Nitric Oxide 2015 Jan;44():88-97
Novel aspects of dietary nitrate and human health.
Weitzberg E, Lundberg JO
Annu. Rev. Nutr. 2013 ;33():129-59
Dietary inorganic nitrate improves mitochondrial efficiency in humans.
Larsen FJ, Schiffer TA, Borniquel S, Sahlin K, Ekblom B, Lundberg JO, et al
Cell Metab. 2011 Feb;13(2):149-59
Nitrate-nitrite-nitric oxide pathway: implications for anesthesiology and intensive care.
Weitzberg E, Hezel M, Lundberg JO
Anesthesiology 2010 Dec;113(6):1460-75