Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals.
Changes in plasma nitrite concentration in the human forearm circulation have recently been shown to reflect acute changes in endothelial nitric oxide synthase (eNOS)-activity. Whether basal plasma nitrite is a general marker of constitutive NOS-activity in vivo is yet unclear. Due to the rapid metabolism of nitrite in blood and the difficulties in its analytical determination literature data on levels of nitrite in mammals are largely inconsistent. We hypothesized that constitutive NOS-activity in the circulatory system is relatively uniform throughout the mammalian kingdom. If true, this should result in comparable systemic plasma nitrite levels in different species. Using three different analytical approaches we determined plasma nitrite concentration to be in a nanomolar range in a variety of species: humans (305 +/- 23 nmol/l), monkeys (367 +/- 62 nmol/l), minipigs (319 +/- 24 nmol/l), dogs (305 +/- 50 nmol/l), rabbits (502 +/- 21 nmol/l), guinea pigs (412 +/- 44 nmol/l), rats (191 +/- 43 nmol/l), and mice (457 +/- 51 nmol/l). Application of different NOS-inhibitors in humans, minipigs, and dogs decreased NOS-activity and thereby increased vascular resistance. This was accompanied by a significant, up to 80%, decrease in plasma nitrite concentration. A comparison of plasma nitrite concentrations between eNOS(-/-) and NOS-inhibited wild-type mice revealed that 70 +/- 5% of plasma nitrite is derived from eNOS. These results provide evidence for a uniform constitutive vascular NOS-activity across mammalian species.
Department of Medicine, Division of Cardiology, Pulmonary Diseases, Angiology, Heinrich-Heine-University, Duesseldorf, Germany.
Petra
P
Kleinbongard
André
A
Dejam
Thomas
T
Lauer
Tienush
T
Rassaf
Achim
A
Schindler
Olaf
O
Picker
Thomas
T
Scheeren
Axel
A
Gödecke
Jürgen
J
Schrader
Rainer
R
Schulz
Gerd
G
Heusch
Günter A
GA
Schaub
Nathan S
NS
Bryan
Martin
M
Feelisch
Malte
M
Kelm
D000818:Animals; D004285:Dogs; D006801:Humans; D007269:Injections, Intra-Arterial; D008322:Mammals; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009573:Nitrites / Q000097:blood*; D012680:Sensitivity and Specificity; D013552:Swine; D014655:Vascular Resistance; D019323:omega-N-Methylarginine / Q000494:pharmacology
D009566:Nitrates; D009573:Nitrites; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester