Journal article
Downregulation of propranolol-sensitive β-adrenoceptor signaling after inhibition of nitric oxide synthesis
British journal of pharmacology, Vol.147(7), pp.755-764
2006
DOI: 10.1038/sj.bjp.0706675
PMCID: PMC1752012
PMID: 16906168
Abstract
1 The β-adrenoceptor agonist, isoprenaline, elicits vasodilation and tachycardia in anesthetized rats via activation of propranolol-sensitive β1- and β2-adrenoceptors and also by propranolol-insensitive β1- and β3- adrenoceptors. 2 The aim of this study was to determine whether the relative contribution of propranolol-sensitive and -insensitive β-adrenoceptors to the changes in heart rate (HR) and vascular resistances elicited by isoprenaline is altered after blockade of nitric oxide (NO) synthase, in pentobarbital-anesthetized rats. 3 The hemodynamic responses elicited by isoprenaline (0.1 and 0.5 μg kg-1, i.v.) were determined before and after injection of saline or the NO synthase inhibitor, N G-nitro-L-arginine methylester (L-NAME, 50 μmol kg-1, i.v.), and again after injection of the β1- and β2-adrenoceptor antagonist, propranolol (1 mg kg-1, i.v.). The responses elicited by the above doses of isoprenaline were also determined before and during infusion of the α1-adrenoceptor agonist, phenylephrine (3 μg kg-1 min-1, i.v.), and again 15-20 min after injection of propranolol (1.0 mg kg-1, i.v.). 4 Both doses of isoprenaline elicited tachycardia and reductions in vascular resistances. Propranolol eliminated the responses elicited by the lower dose of isoprenaline and substantially diminished the responses elicited by the higher dose of the β1-, β2- and β3- adrenoceptor agonist. The maximal vasodilator responses elicited by both doses of isoprenaline were not diminished whereas the maximal increases in HR were higher after injection of L-NAME. The ability of propranolol to diminish the hemodynamic actions of isoprenaline was substantially diminished in L-NAME-treated rats, whereas propranolol retained its potency in rats that received an equi-pressor infusion of the α1-adrenoceptor agonist, phenylephrine. 5 The finding that the maximal vasodilator responses elicited by isoprenaline were not diminished by L-NAME suggests that the vasodilation elicited by this drug was due to direct activation of β-adrenoceptors on vascular smooth muscle and that the full compliment of isoprenaline-sensitive receptors was not changed after inhibition of NO synthesis. However, these results suggest that the activities of propranolol-sensitive β-adrenoceptors are downregulated, whereas propranolol-insensitive β-adrenoceptors are upregulated upon the loss of exposure to endothelial nitrosyl factors. © 2006 Nature Publishing Group All rights reserved.
Details
- Title: Subtitle
- Downregulation of propranolol-sensitive β-adrenoceptor signaling after inhibition of nitric oxide synthesis
- Creators
- Erin J Whalen - Department of Pharmacology, University of Iowa, Iowa City, IA, United StatesJames N Bates - Department of Anesthesia, University of Iowa, Iowa City, IA, United StatesAlan Kim Johnson - Department of Pharmacology, University of Iowa, Iowa City, IA, United StatesStephen J Lewis - Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389, United States
- Resource Type
- Journal article
- Publication Details
- British journal of pharmacology, Vol.147(7), pp.755-764
- Publisher
- Nature Publishing
- DOI
- 10.1038/sj.bjp.0706675
- PMID
- 16906168
- PMCID
- PMC1752012
- ISSN
- 0007-1188
- eISSN
- 1476-5381
- Language
- English
- Date published
- 2006
- Academic Unit
- Psychological and Brain Sciences; Anesthesia; Neuroscience and Pharmacology; Health and Human Physiology
- Record Identifier
- 9984213432102771
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