Journal article
Inhibition of adrenergic vasoconstriction by quinidine
The Journal of pharmacology and experimental therapeutics, Vol.188(1), pp.124-134
01/1974
DOI: 10.1016/S0022-3565(25)29732-4
PMID: 4358435
Abstract
Experiments were done to investigate the effects of quinidine on responses to adrenergic vasoconstrictor stimuli in dogs and humans. In dogs, gracilis muscle and hindpaw were isolated, denervated and perfused with arterial blood at constant flows. Three groups of dogs were studied : eight dogs received intravenous infusions of quinidine, 1.25 mg/kg; eight received quinidine, 5 mg/kg; and eight received the vehicle alone. Serum levels of quinidine were in the therapeutic range, 2.1 to 5.5 mg/l. Intravenous quinidine markedly reduced vasoconstrictor responses to sympathetic stimulation and to norepinephrine in both muscle and paw. Vasoconstrictor responses to the nonadrenergic agonists, angiotensin and 5-hydroxytryptamine, were not reduced. Intra-arterial infusions of quinidine also reduced constrictor responses to adrenergic stimuli but not to nonadrenergic agonists. Decreases in vasoconstrictor responses to adrenergic stimuli did not result from augmentation of beta receptor-mediated or neurogenic cholinergic vasodilatation, since vasodilator responses to isoproterenol were not increased after quinidine and responses to nerve stimulation were inhibited in the atropine-treated muscle. In another group of dogs, intra-arterial injections of quinidine and glyceryl trinitrate were given in doses which produced equivalent vasodilatation in denervated muscle and paw. When the same doses were injected into the contralateral innervated beds quinidine produced greater vasodilatation than glyceryl trinitrate. In man, quinidine levels of 1.2 mg/l caused vasodilatation in forearms of six to eight subjects and significantly reduced constrictor responses to intravenous norepinephrine and to lower body negative pressure. The results indicate that quinidine interferes selectively with vasoconstrictor stimuli which activate alpha adrenergic receptors and suggest that this mechanism as well as a direct vasodilator effect may contribute to vasodilatation and hypotension.
Details
- Title: Subtitle
- Inhibition of adrenergic vasoconstriction by quinidine
- Creators
- Phillip G SchmidLoren D NelsonAllyn L MarkDonald D HeistadFrancois M Abboud
- Resource Type
- Journal article
- Publication Details
- The Journal of pharmacology and experimental therapeutics, Vol.188(1), pp.124-134
- Publisher
- United States
- DOI
- 10.1016/S0022-3565(25)29732-4
- PMID
- 4358435
- ISSN
- 0022-3565
- eISSN
- 1521-0103
- Language
- English
- Date published
- 01/1974
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Pharmacy Practice and Science; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984025432602771
Metrics
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