| Cyclooxygenase inhibition and baroreflex sensitivity in humans. | |
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MedLine Citation:
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PMID: 15486039 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Animal studies suggest that prostanoids (i.e., such as prostacyclin) may sensitize or impair baroreceptor and/or baroreflex responsiveness depending on the site of administration and/or inhibition. We tested the hypothesis that acute inhibition of cyclooxygenase (COX), the rate-limiting enzyme in prostanoid synthesis, impairs baroreflex regulation of cardiac period (R-R interval) and muscle sympathetic nerve activity (MSNA) in humans and augments pressor reactivity. Baroreflex sensitivity (BRS) was determined at baseline (preinfusion) and 60 min after (postinfusion) intravenous infusion of a COX antagonist (ketorolac; 45 mg) (24 +/- 1 yr; n = 12) or saline (25 +/- 1 yr; n = 12). BRS was assessed by using the modified Oxford technique (bolus intravenous infusion of nitroprusside followed by phenylephrine). BRS was quantified as the slope of the linear portion of the 1) R-R interval-systolic blood pressure relation (cardiovagal BRS) and 2) MSNA-diastolic blood pressure relation (sympathetic BRS) during pharmacological changes in arterial blood pressure. Ketorolac did not alter cardiovagal (19.4 +/- 2.1 vs. 18.4 +/- 2.4 ms/mmHg preinfusion and postinfusion, respectively) or sympathetic BRS (-2.9 +/- 0.7 vs. -2.6 +/- 0.4 arbitrary units.beat(-1).mmHg(-1)) but significantly decreased a plasma biomarker of prostanoid generation (plasma thromboxane B2) by 53 +/- 11%. Cardiovagal BRS (21.3 +/- 3.8 vs. 21.2 +/- 3.0 ms/mmHg), sympathetic BRS (-3.4 +/- 0.3 vs. -3.2 +/- 0.2 arbitrary units.beat(-1).mmHg(-1)), and thromboxane B2 (change in -1 +/- 12%) were unchanged in the control (saline infusion) group. Pressor responses to steady-state incremental (0.5, 1.0, and 1.5 microg.kg(-1).min(-1)) infusion (5 min/dose) of phenylephrine were not altered by ketorolac (n = 8). Collectively, these data indicate that acute pharmacological antagonism of the COX enzyme does not impair BRS (cardiovagal or sympathetic) or augment pressor reactivity in healthy young adults. |
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Authors:
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Kevin D Monahan; Chester A Ray |
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Publication Detail:
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Type: Clinical Trial; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2004-10-14 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 288 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2005 Feb |
Date Detail:
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Created Date: 2005-01-14 Completed Date: 2005-02-23 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H737-43 Citation Subset: IM; S |
Affiliation:
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Department of Medicine (Cardiology), General Clinical Research Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033-2390, USA. kmonahan@psu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Baroreflex / drug effects*, physiology Blood Pressure / drug effects*, physiology Cyclooxygenase Inhibitors / administration & dosage* Female Humans Infusions, Intravenous Ketorolac / administration & dosage* Male Prostaglandins / metabolism Sympathetic Nervous System / drug effects, physiology Vagus Nerve / drug effects, physiology |
| Grant Support | |
ID/Acronym/Agency:
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C06 RR-016499/RR/NCRR NIH HHS; CA-00207/CA/NCI NIH HHS; DC-006459/DC/NIDCD NIH HHS; HL-58503/HL/NHLBI NIH HHS; HL-67624/HL/NHLBI NIH HHS; M01 RR-10732/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclooxygenase Inhibitors; 0/Prostaglandins; 66635-83-4/Ketorolac |
| Investigator | |
Investigator/Affiliation:
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C A Ray / PA St U Coll Med, Hershey |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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