Document Detail


Cyclooxygenase inhibition and baroreflex sensitivity in humans.
MedLine Citation:
PMID:  15486039     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Kevin D Monahan; Chester A Ray
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Publication Detail:
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:
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:
Created Date:  2005-01-14     Completed Date:  2005-02-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H737-43     Citation Subset:  IM; S    
Affiliation:
Department of Medicine (Cardiology), General Clinical Research Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033-2390, USA. kmonahan@psu.edu
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MeSH Terms
Descriptor/Qualifier:
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:
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:
0/Cyclooxygenase Inhibitors; 0/Prostaglandins; 66635-83-4/Ketorolac
Investigator
Investigator/Affiliation:
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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