Document Detail


Further characterization of the cardiovascular effects of the dopamine beta-hydroxylase inhibitor SK&F 102698 in conscious hypertensive rats.
MedLine Citation:
PMID:  3050029     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The dopamine beta-hydroxylase inhibitor SK&F 102698 was characterized by studying its cardiovascular effects in hypertensive rats. The antihypertensive effects of SK&F 102698 (50 mg/kg p.o.) were studied in three different rat models of hypertension. In spontaneously hypertensive and deoxycorticosterone acetate-salt rats SK&F 102698 produced blood pressure reductions of approximately 21 and 23%, respectively. In contrast, SK&F 102698 did not produce a significant decrease in blood pressure in 2-kidney, 1-clip Goldblatt hypertensive rats. The antihypertensive mechanism of action of dopamine beta-hydroxylase inhibition was probed with the selective DA1-receptor antagonist SCH 23390, which produced an attenuation of the antihypertensive effects of SK&F 102698. Experiments were designed to separate the peripheral from the central components of the cardiovascular effects of SK&F 102698. In spinal cord stimulated pithed spontaneously hypertensive rats, SK&F 102698 reduced blood pressure but not heart rate, indicating a peripherally mediated vasodilation and a centrally mediated heart rate effect. Furthermore, when SK&F 102698 was administered directly into the fourth ventricle of conscious spontaneously hypertensive rats, a pronounced bradycardia and lowering of blood pressure was observed. SCH 23390 (200 micrograms/kg i.v.) and l-sulpiride (1 mg/kg i.v.) inhibited the cardiovascular effects of SK&F 102698 administered into the fourth ventricle. These data indicate that inhibition of dopamine beta-hydroxylase with SK&F 102698 results in both peripherally and centrally mediated cardiovascular effects and suggest that central dopamine receptors contribute to the control of systemic blood pressure in hypertensive models associated with an increased sympathetic outflow.
Authors:
E H Ohlstein; L I Kruse; M Ezekiel; R N Willette
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  247     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1988 Oct 
Date Detail:
Created Date:  1988-11-18     Completed Date:  1988-11-18     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  186-95     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, Pennsylvania.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antihypertensive Agents / pharmacology*
Atropine / pharmacology
Benzazepines / pharmacology
Blood Pressure / drug effects*
Brain / drug effects
Dopamine beta-Hydroxylase / antagonists & inhibitors*
Heart Rate / drug effects
Imidazoles / pharmacology*
Male
Rats
Rats, Inbred SHR
Receptors, Dopamine / physiology
Chemical
Reg. No./Substance:
0/1-(3,5-difluorobenzyl)imidazole-2-thiol; 0/Antihypertensive Agents; 0/Benzazepines; 0/Imidazoles; 0/Receptors, Dopamine; 51-55-8/Atropine; EC 1.14.17.1/Dopamine beta-Hydroxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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