| Endogenous nitric oxide contributes to bradykinin-stimulated glucose uptake but attenuates vascular tissue-type plasminogen activator release. | |
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MedLine Citation:
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PMID: 19841473 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bradykinin causes vasodilation, stimulates tissue-type plasminogen activator (t-PA) release and, in rodents, increases muscle glucose uptake. Although bradykinin causes vasodilation partly by activating nitric-oxide synthase (NOS), the role of nitric oxide in regulating bradykinin-stimulated t-PA release is uncertain. This study examined the effect of high-dose NOS inhibition on bradykinin-stimulated t-PA release and glucose uptake in humans. We studied 24 healthy (12 women and 12 men), overweight and obese (body mass index >25 kg/m(2)), normotensive, nondiabetic subjects with normal cholesterol. We measured the effect of intra-arterial N(omega)-monomethyl-L-arginine (L-NMMA, 12 micromol/min) on forearm blood flow (FBF), net t-PA release, and glucose uptake at baseline and in response to intra-arterial bradykinin (50-200 ng/min) in subjects pretreated with the cyclooxygenase inhibitor aspirin. Measurements were repeated after isosorbide dinitrate (ISDN; 5 mg) or sildenafil (50 mg). L-NMMA decreased baseline FBF (P < 0.001), increased baseline forearm vascular resistance (P < 0.001), and increased the t-PA arterial-venous gradient (P = 0.04) without affecting baseline net t-PA release or glucose uptake. During L-NMMA, ISDN tended to decrease baseline net t-PA release (P = 0.06). L-NMMA blunted bradykinin-stimulated vasodilation (P < 0.001 for FBF and FVR). Bradykinin increased net glucose extraction (from -80 +/- 23 to -320 +/- 97 microg/min/100 ml at 200 ng/min bradykinin, P = 0.02), and L-NMMA (-143 +/- 50 microg/min/100 ml at 200 ng/min, P = 0.045) attenuated this effect. In contrast, L-NMMA enhanced bradykinin-stimulated t-PA release (39.9 +/- 7.0 ng/min/100 ml versus 30.0 +/- 4.2 ng/min/100 ml at 200 ng/min, P = 0.04 for L-NMMA). In gender-stratified analyses, L-NMMA significantly increased bradykinin-stimulated t-PA release in women (F = 6.7, P = 0.02) but not in men. Endogenous NO contributes to bradykinin-stimulated vasodilation and glucose uptake but attenuates the fibrinolytic response to exogenous bradykinin. |
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Authors:
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Mias Pretorius; Nancy J Brown |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-10-19 |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 332 ISSN: 1521-0103 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2009-12-21 Completed Date: 2010-01-26 Revised Date: 2011-07-19 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
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Languages: eng Pagination: 291-7 Citation Subset: IM |
Affiliation:
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Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. mias.pretorius@vanderbilt.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aspirin / pharmacology Bradykinin / pharmacology*, physiology Dose-Response Relationship, Drug Endothelium, Vascular / metabolism*, physiopathology Enzyme Inhibitors / pharmacology Female Forearm / blood supply Glucose / metabolism* Humans Male Nitric Oxide / biosynthesis, physiology* Nitric Oxide Donors / pharmacology Nitric Oxide Synthase / antagonists & inhibitors Obesity / enzymology, metabolism*, physiopathology Regional Blood Flow / physiology Tissue Plasminogen Activator / metabolism* Vasodilation / drug effects, physiology omega-N-Methylarginine / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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1UL1-RR024975/RR/NCRR NIH HHS; HL060906/HL/NHLBI NIH HHS; HL065193/HL/NHLBI NIH HHS; HL085740/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Nitric Oxide Donors; 10102-43-9/Nitric Oxide; 17035-90-4/omega-N-Methylarginine; 50-78-2/Aspirin; 50-99-7/Glucose; 58-82-2/Bradykinin; EC 1.14.13.39/Nitric Oxide Synthase; EC 3.4.21.68/Tissue Plasminogen Activator |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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