Influence of Dietary Nitrate on Vascular Dysfunction and Inflammation

We wish to determine in a prospective manner whether inorganic nitrate affects the endothelial dysfunction induced by systemic inflammation. At baseline we will measure flow-mediated dilatation (FMD) and peripheral augmentation index, as well as aortic stiffness, as measured by pulse wave velocity (PWV). Volunteers will then receive ~8 mmols of dietary nitrate or nitrate free placebo juice once daily for 6 days. After this, depending on availability, volunteers will receive a typhoid vaccine Typherix®, GlaxoSmithKline UK or Typhim Vi ™, AAH Pharmaceuticals Ltd). This vaccine generates a mild systemic inflammation that is associated with vascular dysfunction. All vascular function measures will be repeated at 8 hours and 32 hours after vaccine administration.

Inclusion criteria

• Healthy volunteers
• Aged 18-45
• Volunteers who are willing to sign the consent form.
• Normal resting blood pressure (<140/90 mmHg)

Exclusion criteria

• Healthy subjects unwilling to consent
• Pregnant, or any possibility that a subject may be pregnant unless in the latter case a pregnancy test is performed with a negative result
• History of any serious illnesses, including recent infections or trauma
• Subjects taking systemic medication (other than the oral contraceptive pill)
• Subjects with self-reported use of mouthwash or tongue scrapes
• Subjects with recent (3 months) or current antibiotic use
• Subjects with a history, or recent treatment of (within last 3 months) any oral condition (excluding caries), including gingivitis, periodontitis and halitosis
• Subjects with a history of typhoid vaccination in the last 6 months
• Subjects with any history of a blood-borne infectious disease such Hepatitis B or C virus, or HIV