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.
Kleinbongard
Petra
P
Department of Medicine, Division of Cardiology, Pulmonary Diseases, Angiology, Heinrich-Heine-University, Duesseldorf, Germany.
Dejam
André
A
Lauer
Thomas
T
Rassaf
Tienush
T
Schindler
Achim
A
Picker
Olaf
O
Scheeren
Thomas
T
Gödecke
Axel
A
Schrader
Jürgen
J
Schulz
Rainer
R
Heusch
Gerd
G
Schaub
Günter A
GA
Bryan
Nathan S
NS
Feelisch
Martin
M
Kelm
Malte
M
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