title: NO metabolite flux across the human coronary circulation.
abstract: OBJECTIVE
  The theory of a red blood cell derived nitric oxide (NO) reserve conserving NO bioactivity and delivering NO as a function of oxygen demand has been the subject of much interest. We identified the human coronary circulation as an ideal model system in which to analyse NO metabolites because of its large physiological oxygen gradient. Our objective was to identify whether oxygen drove apportion between various NO metabolite species across a single vascular bed.
  
  
  METHODS
  Plasma and red blood cell NO metabolites were assessed from the left main coronary artery, coronary sinus and pulmonary artery (providing cross heart and cross pulmonary analysis) of healthy subjects under resting conditions and following administration of an inhibitor of NO biosynthesis. Physiological parameters and angiographic data were monitored throughout the study.
  
  
  RESULTS
  Under baseline conditions we observed significant metabolite flux upon the transit of blood across the coronary and pulmonary vascular beds. Whilst there was no net loss of NO through the coronary circulation (p=0.0759), plasma nitrite/protein NO (excluding nitrate) (p=0.0279) and red blood cell sulphanilamide labile signal (p=0.0143) decreased whereas haemoglobin-bound NO increased three-fold (p=0.005). These changes across the coronary circulation were reversed through the pulmonary circuit with red blood cell sulphanilamide labile signal (p=0.0143) and plasma nitrite/protein NO (p=0.0279) increasing and haemoglobin-bound NO decreasing. Blockade of NO synthesis increased mean arterial blood pressure (p<0.01) and reduced coronary artery diameter (p<0.05), however we observed similar apportion of NO metabolites across the heart and lung with no net loss or gain in total NO metabolites.
  
  
  CONCLUSIONS
  For the first time in human subjects across the resting coronary circulation we reveal significant re-apportionment of NO between metabolite species which correlate with haemoglobin oxygen saturation. These changes occur even within the transit time of blood across this single vascular bed. We demonstrate no net loss/gain of NO from the total metabolite pool across the coronary circulation even where NO biosynthesis is inhibited.
authors.affiliation: Department of Cardiology, Wales Heart Research Institute, School of Medicine, Cardiff University, Cardiff, CF14 4XN, United Kingdom.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Rogers
authors.forename: Afshin
authors.initials: A
authors.lastname: Khalatbari
authors.forename: Borunendra N
authors.initials: BN
authors.lastname: Datta
authors.forename: Sue
authors.initials: S
authors.lastname: Ellery
authors.forename: Vince
authors.initials: V
authors.lastname: Paul
authors.forename: Michael P
authors.initials: MP
authors.lastname: Frenneaux
authors.forename: Philip E
authors.initials: PE
authors.lastname: James
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D003326:Coronary Circulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004912:Erythrocytes / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D049449:Luminescence; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000097:blood; D010100:Oxygen / Q000097:blood / Q000378:metabolism; D011651:Pulmonary Artery; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D006454:Hemoglobins; D009566:Nitrates; D009573:Nitrites; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010100:Oxygen