Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure

Eur J Appl Physiol. 2016 Sep;116(9):1651-61. doi: 10.1007/s00421-016-3418-7. Epub 2016 Jun 22.


Purpose: Both inorganic nitrate and citrulline are known to alter the arginine-nitric oxide-nitrate system to increase the bioavailability of nitric oxide with potential benefits in the treatment of heart failure. However, their effects on cardiac electrical activity, vascular compliance and peripheral conductance are less well understood. This study examined the effect of nitrate and citrulline on cardiac electrical activity and blood flow.

Methods: Young adult subjects (n = 12) were recruited to investigate the effects of acute oral nitrate consumption (8 mg/kg) and chronic citrulline consumption (3 g/day) on cardiac electrical activity measured by ECG recording and blood pressure. Blood flow and vascular compliance were measured by IR-plethysmography at the thumb and the hallux.

Results: Nitrate (p < 0.05) and citrulline (p < 0.01) consumption both decreased diastolic blood pressure but had no effect on either pulse pressure or rate-pressure product (NS for both). Citrulline also decreased systolic pressure (p < 0.01). Nitrate and citrulline both decreased vascular compliance (p < 0.05 for both) prior to isometric grip exercise, but this was increased for nitrate following exercise (NS). Citrulline decreased R-R interval 9 % (p < 0.05) at rest and increased heart rate (p < 0.05) in addition to significantly decreasing pulse transit duration (6 %; p < 0.05). QRS duration was also decreased by 5 % for citrulline (p < 0.05) with the reduction in R-R interval.

Conclusion: Both nitrate and citrulline supplementation decreased vascular tone at rest but citrulline also altered sympathovagal balance to increase sympathetic tone. We suggest that both oral nitrate and citrulline may be suitable adjuvants for patients with heart failure to improve peripheral tissue oxygenation.

Keywords: Cardiac electrical activity; Citrulline; Nitrate; Vascular compliance.

MeSH terms

  • Administration, Oral
  • Blood Flow Velocity / drug effects
  • Blood Flow Velocity / physiology*
  • Blood Pressure / drug effects
  • Blood Pressure / physiology*
  • Cardiotonic Agents / administration & dosage
  • Citrulline / administration & dosage*
  • Dietary Supplements
  • Dose-Response Relationship, Drug
  • Feasibility Studies
  • Female
  • Heart Failure / drug therapy
  • Heart Failure / physiopathology
  • Heart Rate / drug effects
  • Heart Rate / physiology*
  • Humans
  • Male
  • Nitrates / administration & dosage*
  • Treatment Outcome
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology
  • Vasodilation / drug effects
  • Vasodilation / physiology*


  • Cardiotonic Agents
  • Nitrates
  • Citrulline