Haemodynamic and sympathetic effects of inhibition of nitric oxide synthase by systemic infusion of N(G)-monomethyl-L-arginine into humans are dose dependent

Détails

ID Serval
serval:BIB_F594D056919E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Haemodynamic and sympathetic effects of inhibition of nitric oxide synthase by systemic infusion of N(G)-monomethyl-L-arginine into humans are dose dependent
Périodique
Journal of Hypertension
Auteur(s)
Lepori  M., Sartori  C., Trueb  L., Owlya  R., Nicod  P., Scherrer  U.
ISSN
0263-6352 (Print)
Statut éditorial
Publié
Date de publication
04/1998
Volume
16
Numéro
4
Pages
519-23
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr
Résumé
BACKGROUND: In several animal species, nitric oxide (NO) buffers central neural sympathetic outflow, but data concerning humans are sparse and conflicting. We hypothesized that these conflicting results could be related to large differences in the dose of N(G)-monomethyl-L-arginine, a stereospecific inhibitor of NO synthase, infused in these human studies. OBJECTIVE: To investigate the haemodynamic and sympathetic effects of systemic inhibition of NO synthase by intravenous infusion of two different doses of N(G)-monomethyl-L-arginine into healthy humans and compare these effects with those of an equipressor dose of the non-endothelium-dependent vasoconstrictor phenylephrine. METHODS: Muscle sympathetic nerve activity was measured by microneurography and blood flow by venous occlusion plethysmography. N(G)-monomethyl-L-arginine was infused over 15 min at a rate of 50 microg/kg per min into members of one group (n = 8) and at a rate of 450 microg/kg per min into members of another group (n = 7). An equipressor dose of phenylephrine was infused into four subjects from each group. RESULTS: Infusions of N(G)-monomethyl-L-arginine and of phenylephrine at the higher dose similarly suppressed sympathetic activity. In contrast, infusions of N(G)-monomethyl-L-arginine and of an equipressor dose of phenylephrine at the lower dose had different sympathetic effects. Burst frequency of muscle sympathetic nerve activity remained unchanged during infusion of N(G)-monomethyl-L-arginine but decreased by roughly 50% during infusion of phenylephrine. Infusion of N(G)-monomethyl-L-arginine at both doses did not alter forearm blood flow. Only infusion of N(G)-monomethyl-L-arginine at the higher dose increased forearm vascular resistance. CONCLUSIONS: Haemodynamic and sympathetic effects of inhibition of NO synthase by infusion of N(G)-monomethyl-L-arginine into humans are dose dependent. At higher doses, N(G)-monomethyl-L-arginine exerts sympathoinhibitory effects that are comparable to those evoked by a non-specific vasoconstrictor drug, whereas at lower doses, it exerts sympatho-excitatory effects.
Mots-clé
Adult Dose-Response Relationship, Drug Enzyme Inhibitors/*administration & dosage Hemodynamic Processes/*drug effects/physiology Humans Infusions, Intravenous Male Muscle, Skeletal/blood supply/innervation Nitric Oxide Synthase/antagonists & inhibitors/*physiology Regional Blood Flow/drug effects/physiology Sympathetic Nervous System/*drug effects/physiology omega-N-Methylarginine/*administration & dosage
Pubmed
Web of science
Création de la notice
25/01/2008 15:00
Dernière modification de la notice
20/08/2019 17:22
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