| Inhibition of nitric oxide synthase evokes central sympatho-excitation in healthy humans. | |
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MedLine Citation:
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PMID: 19723781 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Animal studies have indicated that nitric oxide is a key signalling molecule involved in the tonic restraint of central sympathetic outflow from the brainstem. Extension of these findings to humans has been difficult because systemic infusion of nitric oxide synthase (NOS) inhibitors increases blood pressure due to inhibition of endothelial NOS, resulting in activation of the arterial baroreflex and subsequent inhibition of central sympathetic outflow. To overcome this confounding inhibitory influence of the baroreflex, in the current study we directly measured skin sympathetic nerve activity (SNA), which is not under baroreceptor control. Healthy, normotensive humans were studied before, during a 60 min intravenous infusion of the NOS inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME; 4 mg kg(1)), and for 120 min following the infusion (i.e. 180 min total). Skin SNA and arterial blood pressure (BP) were continuously measured. BP was increased from baseline at the end of the l-NAME infusion (14 +/- 2 mmHg; P < 0.05) and remained significantly elevated for the remainder of the experiment (18 +/- 3 mmHg; P < 0.05). Similarly, systemic NOS inhibition produced time-dependent increases in skin SNA, such that skin SNA was elevated at the end of the l-NAME infusion (total activity, 200 +/- 22% baseline; P = 0.08) and was further increased at the end of the study protocol (total activity, 350 +/- 41% baseline; P < 0.05). Importantly, skin SNA remained unchanged during time and hypertensive (phenylephrine) control experiments. These findings indicate that pharmacological inhibition of NOS causes sympathetic activation and support a role of nitric oxide in central sympathetic control in humans. |
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Authors:
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Colin N Young; James P Fisher; Kevin M Gallagher; Adam Whaley-Connell; Kunal Chaudhary; Ronald G Victor; Gail D Thomas; Paul J Fadel |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-09-01 |
Journal Detail:
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Title: The Journal of physiology Volume: 587 ISSN: 1469-7793 ISO Abbreviation: J. Physiol. (Lond.) Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-15 Completed Date: 2010-02-03 Revised Date: 2010-10-18 |
Medline Journal Info:
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Nlm Unique ID: 0266262 Medline TA: J Physiol Country: England |
Other Details:
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Languages: eng Pagination: 4977-86 Citation Subset: IM |
Affiliation:
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Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Blood Pressure / drug effects Central Nervous System / drug effects, enzymology* Enzyme Inhibitors / administration & dosage Female Humans Hypertension / enzymology Infusions, Intravenous Male NG-Nitroarginine Methyl Ester / administration & dosage Nitric Oxide / metabolism Nitric Oxide Synthase / antagonists & inhibitors*, metabolism Skin / drug effects, innervation, metabolism Sympathetic Nervous System / drug effects, enzymology* |
| Grant Support | |
ID/Acronym/Agency:
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DK076636/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 10102-43-9/Nitric Oxide; 50903-99-6/NG-Nitroarginine Methyl Ester; EC 1.14.13.39/Nitric Oxide Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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