Evidence for in vivo transport of bioactive nitric oxide in human plasma
Evidence for in vivo transport of bioactive nitric oxide in human plasma
Although hitherto considered as a strictly locally acting vasodilator, results from recent clinical studies with inhaled nitric oxide (NO) indicate that NO can exert effects beyond the pulmonary circulation. We therefore sought to investigate potential remote vascular effects of intra-arterially applied aqueous NO solution and to identify the mechanisms involved. On bolus application of NO into the brachial artery of 32 healthy volunteers, both diameter of the downstream radial artery and forearm blood flow increased in a dose-dependent manner. Maximum dilator responses were comparable to those after stimulation of endogenous NO formation with acetylcholine and bradykinin. Response kinetics and pattern of NO decomposition suggested that despite the presence of hemoglobin-containing erythrocytes, a significant portion of NO was transported in its unbound form. Infusion of NO (36 micromol/min) into the brachial artery increased levels of plasma nitroso species, nitrite, and nitrate in the draining antecubital vein (by < 2-fold, 30-fold, and 4-fold, respectively), indicative of oxidative and nitrosative chemistry. Infused N-oxides were inactive as vasodilators whereas S-nitrosoglutathione dilated conduit and resistance arteries. Our results suggest that NO can be transported in bioactive form for significant distances along the vascular bed. Both free NO and plasma nitroso species contribute to the dilation of the downstream vasculature.
1241-1248
Rassaf, Tienush
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Preik, Michael
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Kleinbongard, Petra
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Lauer, Thomas
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Heiß, Christian
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Strauer, Bodo-Eckehard
f71dfef9-1bc9-4e85-8944-29e279ba13c5
Feelisch, Martin
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Kelm, Malte
db2bb062-32d7-4b50-9f65-8ba89ffa5f42
1 May 2002
Rassaf, Tienush
a820a375-219a-4fa2-ae10-e77f4b1eb37c
Preik, Michael
59d2d820-b12d-4020-a3a2-b89c636a8ba3
Kleinbongard, Petra
ec93ff61-c3f2-4d2e-a465-59cc949315bb
Lauer, Thomas
57e1e8b6-cfc8-40ac-a946-5ad6e3387477
Heiß, Christian
5cd4df8d-fb5d-4d68-831c-6a186b2a320e
Strauer, Bodo-Eckehard
f71dfef9-1bc9-4e85-8944-29e279ba13c5
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Kelm, Malte
db2bb062-32d7-4b50-9f65-8ba89ffa5f42
Rassaf, Tienush, Preik, Michael, Kleinbongard, Petra, Lauer, Thomas, Heiß, Christian, Strauer, Bodo-Eckehard, Feelisch, Martin and Kelm, Malte
(2002)
Evidence for in vivo transport of bioactive nitric oxide in human plasma.
Journal of Clinical Investigation, 109 (9), .
(doi:10.1172/JCI14995).
(PMID:11994413)
Abstract
Although hitherto considered as a strictly locally acting vasodilator, results from recent clinical studies with inhaled nitric oxide (NO) indicate that NO can exert effects beyond the pulmonary circulation. We therefore sought to investigate potential remote vascular effects of intra-arterially applied aqueous NO solution and to identify the mechanisms involved. On bolus application of NO into the brachial artery of 32 healthy volunteers, both diameter of the downstream radial artery and forearm blood flow increased in a dose-dependent manner. Maximum dilator responses were comparable to those after stimulation of endogenous NO formation with acetylcholine and bradykinin. Response kinetics and pattern of NO decomposition suggested that despite the presence of hemoglobin-containing erythrocytes, a significant portion of NO was transported in its unbound form. Infusion of NO (36 micromol/min) into the brachial artery increased levels of plasma nitroso species, nitrite, and nitrate in the draining antecubital vein (by < 2-fold, 30-fold, and 4-fold, respectively), indicative of oxidative and nitrosative chemistry. Infused N-oxides were inactive as vasodilators whereas S-nitrosoglutathione dilated conduit and resistance arteries. Our results suggest that NO can be transported in bioactive form for significant distances along the vascular bed. Both free NO and plasma nitroso species contribute to the dilation of the downstream vasculature.
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Published date: 1 May 2002
Organisations:
Clinical & Experimental Sciences
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Local EPrints ID: 337866
URI: http://eprints.soton.ac.uk/id/eprint/337866
ISSN: 0021-9738
PURE UUID: e054975f-16bb-4b41-821c-e7967ba4dd19
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Date deposited: 22 Jun 2012 12:38
Last modified: 15 Mar 2024 03:41
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Author:
Tienush Rassaf
Author:
Michael Preik
Author:
Petra Kleinbongard
Author:
Thomas Lauer
Author:
Christian Heiß
Author:
Bodo-Eckehard Strauer
Author:
Malte Kelm
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