Pharmacological nitric oxide research

Recent studies show that the supposedly inert inorganic anions nitrate (NO³¯) and nitrite (NO²¯) can recycle in vivo to form nitric oxide (NO) and other bioactive nitrogen oxides. This represents an important alternative source of NO, 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 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

• Nitrate and nitrite as a substrate for NO generation
• Airway nitric oxide
• NO and the gastrointestinal system
• NO as a marker for inflammation
• Antibacterial effects of nitrite.

Methods

We use most of the standard molecular biology techniques.

In addition, we have numerous highly specialised assays for determination of nitric oxide (NO) in vivo and in vitro. These include chemiluminescence detection of NO in exhaled breath, in nasal air and in intestinal gases (colon, stomach), as well as highly sensitive assays for nitrate, nitrite and S-nitrosothiols, citrulline assay, cGMP RIA, and immunohistochemistry for NOSs.

Collaborations

We collaborate with the research group Nitrate-nitrite-NO pathway in health and disease

Financial support

• Swedish Research Council (VR)
• Torsten Söderberg foundation (site in Swedish)
• Distinguished Professor Award from Karolinska Institutet
• Swedish Heart-Lung foundation
• Vinnova
• Swedish National Centre for Research in Sports (site in Swedish)

Recent publications

Decreased leukocyte recruitment by inorganic nitrate and nitrite in microvascular inflammation and NSAID-induced intestinal injury.
Jädert C, Petersson J, Massena S, Ahl D, Grapensparr L, Holm L, et al
Free Radic. Biol. Med. 2012 Feb;52(3):683-692

Intragastric nitration by dietary nitrite: implications for modulation of protein and lipid signaling.
Rocha BS, Gago B, Barbosa RM, Lundberg JO, Radi R, Laranjinha J
Free Radic. Biol. Med. 2012 Feb;52(3):693-698

Dietary nitrate - a slow train coming.
Weitzberg E, Lundberg JO
J. Physiol. (Lond.) 2011 Nov;589(Pt 22):5333-4

Supplementation with nitrate and nitrite salts in exercise: a word of caution.
Lundberg JO, Larsen FJ, Weitzberg E
J. Appl. Physiol. 2011 Aug;111(2):616-7

Mitochondrial oxygen affinity predicts basal metabolic rate in humans.
Larsen FJ, Schiffer TA, Sahlin K, Ekblom B, Weitzberg E, Lundberg JO
FASEB J. 2011 Aug;25(8):2843-52

Increased plasma and salivary nitrite and decreased bronchial contribution to exhaled NO in pulmonary arterial hypertension.
Malinovschi A, Henrohn D, Eriksson A, Lundberg JO, Alving K, Wikström G
Eur. J. Clin. Invest. 2011 Aug;41(8):889-97

Measurement of luminal nitric oxide in the uterine cavity using a silicon balloon catheter.
Sioutas A, Gemzell-Danielsson K, Lundberg JO, Ehrén I
Nitric Oxide 2011 May;24(4):213-6

Dietary nitrite in nitric oxide biology: a redox interplay with implications for pathophysiology and therapeutics.
Rocha BS, Gago B, Pereira C, Barbosa RM, Bartesaghi S, Lundberg JO, et al
Curr Drug Targets 2011 Aug;12(9):1351-63

Arginase inhibition restores in vivo coronary microvascular function in type 2 diabetic rats.
Grönros J, Jung C, Lundberg JO, Cerrato R, Ostenson CG, Pernow J
Am. J. Physiol. Heart Circ. Physiol. 2011 Apr;300(4):H1174-81