Plasma nitrosothiols contribute to the systemic vasodilator effects of intravenously applied NO: experimental and clinical Study on the fate of NO in human blood.
Higher doses of inhaled NO exert effects beyond the pulmonary circulation. How such extrapulmonary effects can be reconciled with the presumed short half-life of NO in the blood is unclear. Whereas erythrocytes have been suggested to participate in NO transport, the exact role of plasma in NO delivery in humans is not clear. Therefore, we investigated potential routes of NO decomposition and transport in human plasma. NO consumption in plasma was accompanied by a concentration-dependent increase in nitrite and S-nitrosothiols (RSNOs), with no apparent saturation limit up to 200 micro mol/L. The presence of red blood cells reduced the formation of plasma RSNOs. Intravenous infusion of 30 micro mol/min NO in healthy volunteers increased plasma levels of RSNOs and induced systemic hemodynamic effects at the level of both conduit and resistance vessels, as reflected by dilator responses in the brachial artery and forearm microvasculature. Intravenous application of S-nitrosoglutathione, a potential carrier of bioactive NO, mimicked the vascular effects of NO, whereas nitrite and nitrate were inactive. Changes in plasma nitrosothiols were correlated with vasodilator effects after intravenous application of S-nitrosoglutathione and NO. These findings demonstrate that in humans the pharmacological delivery of NO solutions results in the transport and delivery of NO as RSNOs along the vascular tree.
Rassaf
Tienush
T
Department of Medicine, Heinrich-Heine-University, Düsseldorf, Germany.
Kleinbongard
Petra
P
Preik
Michael
M
Dejam
André
A
Gharini
Putrika
P
Lauer
Thomas
T
Erckenbrecht
Julia
J
Duschin
Alexej
A
Schulz
Rainer
R
Heusch
Gerd
G
Feelisch
Martin
M
Kelm
Malte
M
D000328:Adult; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood / Q000494:pharmacology*; D009573:Nitrites / Q000097:blood; D009603:Nitroso Compounds / Q000097:blood*; D026422:S-Nitrosoglutathione / Q000097:blood; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione