| Inhibition of nitric oxide synthase augments myocardial contractile responses to beta-adrenergic stimulation. | |
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MedLine Citation:
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PMID: 8997327 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recent in vitro evidence suggests a role for nitric oxide (NO) in the modulation of myocardial contractility. The specific role of NO in the control of cardiac function in vivo, however, remains unclear. We investigated the effect of NO synthase (NOS) inhibition on myocardial contractility in response to beta-adrenergic stimulation in autonomically blocked dogs. Intracoronary infusions of dobutamine (1-50 micrograms/min) and isoproterenol (0.1 and 0.5 microgram/min) were performed before and after the intracoronary administration of the specific NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Intracoronary dobutamine resulted in a dose-dependent increase in peak first derivative of pressure (dP/dtmax) to a maximum of 195 +/- 10% (P < 0.001). After inhibition of NOS with intracoronary L-NAME at rates of 0.1 and 1 mg/min, the response to dobutamine was significantly enhanced with dP/dtmax, increasing 276 +/- 17 and 317 +/- 26%, respectively (P < 0.001). Intracoronary isoproterenol resulted in a maximum increase in dP/dtmax of 116 +/- 15% (P < 0.001) that further increased to 154 +/- 17 and 157 +/- 18% after NOS inhibition with 0.1 and 1 mg/min L-NAME, respectively (both P < 0.002). L-NAME had no effect on baseline dP/dtmax but did produce a reduction in myocardial guanosine 3',5'-cyclic monophosphate content. These results suggest a role for NO in the control of myocardial contractility in response to beta-adrenergic stimulation in vivo. |
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Authors:
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J F Keaney; J M Hare; J L Balligand; J Loscalzo; T W Smith; W S Colucci |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The American journal of physiology Volume: 271 ISSN: 0002-9513 ISO Abbreviation: Am. J. Physiol. Publication Date: 1996 Dec |
Date Detail:
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Created Date: 1997-02-20 Completed Date: 1997-02-20 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0370511 Medline TA: Am J Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: H2646-52 Citation Subset: IM |
Affiliation:
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Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-Agonists
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pharmacology* Animals Coronary Vessels Cyclic GMP / metabolism Dobutamine / pharmacology Dogs Enzyme Inhibitors / pharmacology Female Heart / drug effects* Injections Isoproterenol / pharmacology Male Myocardial Contraction* Myocardium / metabolism NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide Synthase / antagonists & inhibitors* Ventricular Function |
| Grant Support | |
ID/Acronym/Agency:
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HL-48743/HL/NHLBI NIH HHS; HL-52320/HL/NHLBI NIH HHS; HL-53919/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Agonists; 0/Enzyme Inhibitors; 34368-04-2/Dobutamine; 50903-99-6/NG-Nitroarginine Methyl Ester; 7665-99-8/Cyclic GMP; 7683-59-2/Isoproterenol; 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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