This study is a pharmacodynamic proof of concept study investigating the physiological effects of systemic infusion of nitrite on coronary blood flow using MRI.

This is a healthy volunteer, proof of concept study.

The participant will have blood taken and this will be analysed for baseline levels of nitrate, nitrite and nitroso species. They will then have a baseline MRI to assess coronary flow in normoxia. Next, hypoxia will be induced using 12% oxygen/88% nitrogen. The participant will then have a baseline MRI to assess coronary flow in hypoxia (3 breath-hold image captures).

After all baseline images have been captured, the investigators will commence an intravenous nitrite sodium infusion, dose 70μmol, of 5 minute duration (14μmol /min-1). At the 5th minute, the participant have a further MRI image to assess coronary flow with the intervention in normoxia (3 breath-hold image captures).

A 10-minute washout will follow (with the half-life of nitrite being documented as 110 seconds). There will be optional repeat 3 breath-hold image captures at 5 minutes and at 10 minutes.

Next hypoxia will be induced using 12% oxygen/88% nitrogen again. The investigators will commence a second intravenous nitrite sodium infusion, dose 70μmol, 5 minute duration (14μmol /min-1). At the 5th minute, the participant will have a further MRI image to assess coronary flow with the intervention in hypoxia (3 breath-hold image captures).

At the end of the study the participant will have blood taken and this will be analysed for repeat levels of nitrate, nitrite and nitroso species.

All interventions will be performed by fully trained and competent medical staff.

Inclusion Criteria:

1. Male or female, aged greater than or equal to 18 years
2. Not known to have any significant past medical history and not having regular follow up
3. Able to provide informed consent

Exclusion Criteria:

1. Significant medical, surgical or psychiatric disease that in the opinion of the Clinical Research Fellow would affect subject safety or significantly impact his/her ability to comply with follow-up. This would include any known clotting disorders.
2. Known allergy or intolerance to Nitrites
3. Known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD deficiency detected at screening in males of African, Asian or Mediterranean decent
4. Female subjects must be of non-childbearing potential, defined as follows: postmenopausal females who have had at least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhoea with serum FSH>40mIU/ml or females who have had a hysterectomy, bilateral salpingectomy or bilateral oophorectomy at least 6 weeks prior to enrolment
5. Receipt of an investigational drug or biological agent within the 4 weeks prior to study entry or 5 times the drug half-life, whichever is the longer
6. Predisposed to acute on chronic limb ischemia evident from a history of claudication or known peripheral arterial disease
7. Any contra-indication to MRI, including the presence of an implanted metal device or suspected metal foreign bodies