Journal article
Effects of nitric oxide synthase inhibition on sympathetically-mediated tachycardia
European journal of pharmacology, Vol.365(2), pp.217-223
1999
DOI: 10.1016/S0014-2999(98)00853-X
PMID: 9988105
Abstract
The 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 μmol/kg, iv), 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 μg/kg, iv), produced a pronounced fall in mean arterial blood pressure but only a minor increase in heart rate. The β-adrenoceptor agonist, isoproterenol (0.5 μmol/kg, iv), and the membrane-permeable cAMP analogue, 8-(4-chlorophenylthiol)-cAMP (10 μmol/kg, iv), produced falls in mean arterial blood pressure and pronounced increases in heart rate. The indirectly acting sympathomimetic agent, tyramine (0.5 mg/kg, iv), 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 β
1-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 β
1-adrenoceptor-mediated signal transduction processes in response to the
l-NAME-induced withdrawal of cardiac sympathetic nerve activity.
Details
- Title: Subtitle
- Effects of nitric oxide synthase inhibition on sympathetically-mediated tachycardia
- Creators
- Erin J Whalen - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USAAlan Kim Johnson - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USAStephen J Lewis - Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USA
- Resource Type
- Journal article
- Publication Details
- European journal of pharmacology, Vol.365(2), pp.217-223
- Publisher
- Elsevier B.V
- DOI
- 10.1016/S0014-2999(98)00853-X
- PMID
- 9988105
- ISSN
- 0014-2999
- eISSN
- 1879-0712
- Language
- English
- Date published
- 1999
- Academic Unit
- Psychological and Brain Sciences; Neuroscience and Pharmacology; Health and Human Physiology
- Record Identifier
- 9984213262302771
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