Linked Life Data

15659045

Source:http://linkedlifedata.com/resource/pubmed/id/15659045

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2005-1-20
pubmed:abstractText
1. Activation of dopamine (DA) receptors produces cardiovascular responses such as vasodilation and hypotension. However, knowledge of the role of specific dopamine receptor subtypes (especially D3 and D4) in the cardiovascular system is limited. The objective of the present study was to characterize the haemodynamic and cardiac responses to agonists with selectivity for D1, D2, D3 and D4 receptor subtypes. 2. Inactin-anaesthetized rats were instrumented to measure regional haemodynamic and cardiac contractility responses with slow intravenous infusion of agonists. 3. Fenoldopam (a D1 receptor agonist) decreased (P < 0.05) renal vascular resistance beginning at a dose of 3 micromol/kg. Infusion of PNU-95666E (a D2 receptor agonist) produced dose-dependent decreases (P < 0.05) in mean arterial pressure (MAP), heart rate (HR) and hindquarter vascular resistance (HQVR). Administration of BP897 (a partial D3 receptor agonist) decreased (P < 0.05) MAP and HQVR at 3 micromol/kg. PD168077 (a D4 receptor agonist) caused significant increases in HQVR at 1 micromol/kg. None of the compounds tested elicited significant changes in cardiac contractility. 4. Using selective agonists of dopamine receptor subtypes, the present studies characterize distinct cardiovascular effects in anaesthetized rats. Consistent with its well-defined effects as a D1 receptor agonist, fenoldopam administration resulted in renal vasodilation. Similar to earlier studies using the non-selective D2-like receptor agonist quinpirole, selective agonism at the D2 receptor using PNU-95666E resulted in bradycardia, hindquarter vasodilation and decreases in arterial pressure. Partial agonism at the D3 receptor with BP897 had no effect on heart rate, but did produce depressor responses driven by decreases in HQVR. Conversely, agonism of the D4 receptor using PD168077 resulted in modest hindquarter vasoconstriction that was not dose dependent. Hence, by comparison, agonism of the D4 receptor has little effect in the cardiovascular system of the rat relative to the other dopamine receptor subtype agonists tested.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0305-1870
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
837-41
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Effects of selective dopamine receptor subtype agonists on cardiac contractility and regional haemodynamics in rats.
pubmed:affiliation
Pharmaceutical Discovery, Global Pharmaceutical R&D, Abbott Laboratories, Abbott Park, Illinois 60064-6119, USA. jim.polakowski@abbott.com
pubmed:publicationType
Journal Article, Comparative Study