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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4 Pt 2
|
| pubmed:dateCreated |
1995-5-25
|
| pubmed:abstractText |
Indirect evidence has implicated endothelin-1 in the pathogenesis of hypertension. In the present study we examined such a role directly with SB 209670, a novel nonpeptide endothelin receptor antagonist. The antihypertensive and hemodynamic effects of SB 209670 were examined in conscious, unrestrained spontaneously hypertensive (SHR), normotensive Wistar-Kyoto (WKY), and renin-hypertensive rats. Sustained intravenous infusion of SB 209670 (10 micrograms.kg-1.min-1 for 6 hours) produced a significant, reversible reduction in mean arterial pressure in SHR but not in WKY rats. The antihypertensive response to 10 micrograms.kg-1.min-1 SB 209670 (approximately 25 mm Hg reduction in blood pressure) was associated with bradycardia (16% decrease in heart rate) but only a minimal reduction (3%) in cardiac output, because stroke volume was evaluated (by 15%). Therefore, the antihypertensive effect of SB 209670 resulted from a decrease (13%) in total peripheral resistance. A sustained antihypertensive effect could also be observed after intraduodenal administration of SB 209670 (3 mg/kg) in conscious SHR (reduction of approximately 35 mm Hg 5 hours after administration). SB 209670 (3 mg/kg intravenous bolus) did not alter the pressor response or tachycardia observed in pithed SHR after stimulation of thoracolumbar sympathetic outflow. SB 209670 was also antihypertensive in renin-hypertensive rats, lowering blood pressure to an extent similar to that observed in SHR. Thus, the data presented provide evidence to support a role for endothelin-1 in the pathophysiology of two animal models of hypertension.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antihypertensive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Indans,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Endothelin,
http://linkedlifedata.com/resource/pubmed/chemical/Renin,
http://linkedlifedata.com/resource/pubmed/chemical/SB 209670
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0194-911X
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
25
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
818-22
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:7721437-Animals,
pubmed-meshheading:7721437-Antihypertensive Agents,
pubmed-meshheading:7721437-Dose-Response Relationship, Drug,
pubmed-meshheading:7721437-Duodenum,
pubmed-meshheading:7721437-Electric Stimulation,
pubmed-meshheading:7721437-Heart Rate,
pubmed-meshheading:7721437-Hypertension,
pubmed-meshheading:7721437-Indans,
pubmed-meshheading:7721437-Injections,
pubmed-meshheading:7721437-Injections, Intravenous,
pubmed-meshheading:7721437-Male,
pubmed-meshheading:7721437-Rats,
pubmed-meshheading:7721437-Rats, Inbred SHR,
pubmed-meshheading:7721437-Rats, Inbred WKY,
pubmed-meshheading:7721437-Rats, Sprague-Dawley,
pubmed-meshheading:7721437-Receptors, Endothelin,
pubmed-meshheading:7721437-Renin,
pubmed-meshheading:7721437-Sympathetic Nervous System
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Antihypertensive actions of the novel nonpeptide endothelin receptor antagonist SB 209670.
|
| pubmed:affiliation |
Department of Cardiovascular Pharmacology (UW 2510), SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
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| pubmed:publicationType |
Journal Article
|