Effects of SR 49059, a new orally active and specific vasopressin V1 receptor antagonist, on vasopressin-induced vasoconstriction in humans

Details

Serval ID
serval:BIB_39BE78C8506E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Effects of SR 49059, a new orally active and specific vasopressin V1 receptor antagonist, on vasopressin-induced vasoconstriction in humans
Journal
Hypertension
Author(s)
Weber  R., Pechere-Bertschi  A., Hayoz  D., Gerc  V., Brouard  R., Lahmy  J. P., Brunner  H. R., Burnier  M.
ISSN
0194-911X (Print)
Publication state
Published
Issued date
11/1997
Volume
30
Number
5
Pages
1121-7
Notes
Clinical Trial
Journal Article
Randomized Controlled Trial --- Old month value: Nov
Abstract
We have evaluated the efficacy of SR 49059, a new orally active and specific vasopressin V1 receptor antagonist (arginine-vasopressin [AVP]), in the blockade of the vascular effects of exogenous AVP in healthy subjects. In preliminary experiments, two procedures to measure the V1 vascular effects of AVP were assessed. First, the AVP-induced changes in skin blood flow were investigated by the injection of increasing doses of AVP intradermally, with or without a previous local vasodilation with calcitonin gene-related peptide (CGRP). In a second protocol, AVP was infused intra-arterially, and the changes in radial artery diameter and blood flow were measured. The intradermal injection of AVP caused significant decreases in skin blood flow, and the use of CGRP increased the sensitivity of the method by a factor of 10(2) to 10(3). AVP infused intra-arterially caused dose-dependent decreases in the radial artery diameter and blood flow. In the main study, the potency and efficacy of SR 49059 to block the AVP-induced changes in skin blood flow were assessed in 12 healthy men with a double-blind, triple crossover study design. The subjects were randomized to receive a placebo orally and 30 mg and 300 mg of the antagonist at a 1-week interval. The subjects were then further randomized to evaluate the efficacy of the same doses of the antagonist to block the vasoconstriction of the radial artery induced by an intra-arterial infusion of AVP. SR 49059 inhibits, dose-dependently and significantly, the AVP-induced changes in skin blood flow, with a peak effect occurring between 2 and 6 hours after injection. In addition, the 300-mg dose of SR 49059 completely blocked the vasoconstriction of the radial artery induced by AVP. In conclusion, skin blood-flow measurement, after intradermal injection of AVP on a skin area vasodilated with CGRP, is an effective method to investigate the V1 vascular effect of AVP in humans. SR 49059 is a potent and specific antagonist of V1 receptors, which blocks the AVP-induced vasoconstriction.
Keywords
Administration, Oral Adult Arginine Vasopressin/*pharmacology Calcitonin Gene-Related Peptide/pharmacology Double-Blind Method Forearm Hormone Antagonists/*pharmacology Humans Indoles/*pharmacology Injections, Intra-Arterial Injections, Intradermal Male Pyrrolidines/*pharmacology Radial Artery/drug effects/physiology Receptors, Vasopressin/*antagonists & inhibitors Reference Values Regional Blood Flow/drug effects Skin/blood supply Vasoconstriction/*drug effects
Pubmed
Web of science
Create date
17/01/2008 16:38
Last modification date
20/08/2019 13:29
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