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Effects of nitric oxide synthase inhibition on sympathetically-mediated tachycardiaThe aim of the present study was to determine whether inhibition of nitric oxide (NO) synthesis directly alters the tachycardia produced by sympathetically-derived norepinephrine. The NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 50 micromol/kg, i.v.), produced a marked rise in mean arterial blood pressure. This pressor response was associated with a fall in heart rate which involved the withdrawal of cardiac sympathetic nerve activity. The NO-donor, sodium nitroprusside (5 microg/kg, i.v.), produced a pronounced fall in mean arterial blood pressure but only a minor increase in heart rate. The beta-adrenoceptor agonist, isoproterenol (0.5 micromol/kg, i.v.), and the membrane-permeable cAMP analogue, 8-(4-chlorophenylthiol)-cAMP (10 micromol/kg, i.v.), produced falls in mean arterial blood pressure and pronounced increases in heart rate. The indirectly acting sympathomimetic agent, tyramine (0.5 mg/kg, i.v.), produced a pressor response and a tachycardia. The effects of sodium nitroprusside, tyramine, isoproterenol and 8-(4-chlorophenylthiol)-cAMP on mean arterial blood pressure were not markedly affected by L-NAME. However, the tachycardia produced by these agents was considerably exaggerated in the presence of this NO synthesis inhibitor. These findings suggest that L-NAME potentiates the tachycardia produced by sympathetically-derived norepinephrine. The increased responsiveness to norepinephrine may involve (i) a rapid up-regulation of cardiac beta1-adrenoceptors and cAMP signaling in cardiac pacemaker cells due to the loss of the inhibitory influence of cardiac NO, and (ii) the up-regulation of beta1-adrenoceptor-mediated signal transduction processes in response to the L-NAME-induced withdrawal of cardiac sympathetic nerve activity.
Document ID
20040142080
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Whalen, E. J.
(University of Iowa Iowa City, 52242-1109, United States)
Johnson, A. K.
Lewis, S. J.
Date Acquired
August 22, 2013
Publication Date
January 22, 1999
Publication Information
Publication: European journal of pharmacology
Volume: 365
Issue: 3-Feb
ISSN: 0014-2999
Subject Category
Life Sciences (General)
Report/Patent Number
ISSN: 0014-2999
Funding Number(s)
CONTRACT_GRANT: HL-14388
CONTRACT_GRANT: HL-57472
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Regulatory Physiology
Non-NASA Center
Norepinephrine/pharmacology
NG-Nitroarginine Methyl Ester/pharmacology
Arrhythmia/chemically induced
Nitric-Oxide Synthase/biosynthesis
Vasomotor System/physiology
Blood Pressure/drug effects
Rats
Drug Synergism
Support, U.S. Gov't, Non-P.H.S
Male
Atropine/pharmacology
Rats, Sprague-Dawley
Tyramine/pharmacology
Animals
Anesthesia
Propranolol/pharmacology
Support, U.S. Gov't, P.H.S
Nitroprusside/pharmacology
Cyclic AMP/analogs & derivatives
Isoproterenol/pharmacology
Drug Interactions

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