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.
A major focus is to explore the role of the nitrate-nitrite-NO pathway for the generation of nitric oxide and other reactive nitrogen intermediates in mammals. Recent studies show that the inorganic anions nitrate (NO³¯) and nitrite (NO²¯) can recycle in vivo to form nitric oxide and other bioactive nitrogen oxides. This represents an important alternative source of nitric oxide, especially during hypoxia 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 diseases such as myocardial infarction, stroke, systemic and pulmonary hypertension and gastric ulceration.
Projects
1. Bioactivation of dietary nitrate and mechanism of action
Oral commensal bacteria are important for bioactivation of nitrate to nitrite. In experimental models, as well as in human studies, we explore the role of oral bacteria in nitrate bioactivation as well as in regulation cardiovascular and metabolic function.
2. Nitrate, inflammation and oxidative stress
Dietary nitrate and nitrite have anti-inflammatory and antioxidant properties. This is studied in experimental models and in humans. We aim to investigate the mechanism underlying these effects in health and disease.
3. Nitrate-nitrite-NO pathway and mitochondrial function
Dietary nitrate improve mitochondrial function by affecting proteins involved in mitochondrial uncoupling. These findings can explain the beneficial effects of dietary nitrate on exercise performance. Further studies are underway to investigate the effects of nitrate and nitrite on mitochondrial function.
4. Dietary nitrate and exercise physiology
We have shown that dietary nitrate reduce oxygen cost during physical exercise in humans, and we are now using experimental models to investigate the underlying mechanisms. Apart from improved mitochondrial function we have recently collaborated with the Westerblad research group at Karolinska Institutet to show increased skeletal muscle contractility after dietary nitrate.
5. Effects of dietary nitrate on ischemia/reperfusion injury
In experimental and clinical studies we investigate if the nitrate-nitrite-NO pathway can be harnessed therapeutically in conditions of ischemia-reperfusion injury (IR-injury) in the heart and kidney. IR-injury is common in relation to trauma, surgery and intensive care and the ongoing studies may lead to novel therapeutic suggestions in these patient groups.
Collaboration
We collaborate with the Pharmacological nitric oxide research group at the Department of Physiology and Pharmacology.
Financial support
- Swedish Research Council (VR)
- Swedish Heart and Lung Foundation
- Torsten Söderberg's foundation (site in Swedish)
- Stockholm County Council (ALF)
Group members
Karin Ericson – PhD student
Halla Halldorsdottir – PhD student
Jon Lundberg – Professor
Carina Nihlen – Biomedical scientist
Annika Olsson – Biomedical scientist
Michaela Sundqvist – PhS student
Eddie Weitzberg – Professor, research group leader