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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-3
|
| pubmed:dateCreated |
1996-1-18
|
| pubmed:abstractText |
The angiotensin II antagonistic activity of SB 203220, [E-alpha-[[2-butyl-1-(4-carboxy-1-naphthalenyl)methyl]-1H- imidazol-5-yl]-methylene]-2-thiophene-propanic acid], was examined in several in vitro and in vivo assays. SB 203220 displaced [125I]angiotensin II binding from a variety of tissues including the cloned human AT1 receptor (IC(50)5-15 nM). SB 203220 (10 microM) did not interact with AT2, endothelin (ETA and ETB) or calcitonin gene-related peptide receptors. [3H]SB 203220 bound with high affinity to the AT1 receptor (Kd = 4.9 nM), but dissociated from the receptor at a much slower rate when compared to [3H]SK&F 108566. SB 203220 antagonized intracellular Ca2+ mobilization induced by angiotensin II in rat vascular smooth muscle cells and exhibited a selective and partially insurmountable antagonism of angiotensin II-induced contraction in isolated rabbit aorta. In the aorta, SB 203220 produced a concentration-dependent parallel shift in the concentration-response curve to angiotensin II [EC30 = 5.94 +/- 1.6 10(-11) M] and depressed the maximal contractile response to angiotensin II by approximately 35%. The antagonistic effect of SB 203220 in rabbit aorta was slowly reversible compared to SK&F 108566. SB 203220 displayed no agonist activity and had no effect on the contractile responses to KCl, endothelin-1 or norepinephrine. In rats, SB 203220 at 10 mg/kg i.v. inhibited angiotensin II-induced aldosterone release. Intraduodenal or oral administration of SB 203220 (1-10 mg/kg) to conscious rats and dogs inhibited the pressor responses to exogenous angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin Receptor Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Antihypertensive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/SB 203220,
http://linkedlifedata.com/resource/pubmed/chemical/Thiophenes
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0014-2999
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
5
|
| pubmed:volume |
283
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
63-72
|
| pubmed:dateRevised |
2010-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:7498322-Angiotensin II,
pubmed-meshheading:7498322-Angiotensin Receptor Antagonists,
pubmed-meshheading:7498322-Animals,
pubmed-meshheading:7498322-Antihypertensive Agents,
pubmed-meshheading:7498322-Aorta,
pubmed-meshheading:7498322-Binding, Competitive,
pubmed-meshheading:7498322-Calcium,
pubmed-meshheading:7498322-Cattle,
pubmed-meshheading:7498322-Dogs,
pubmed-meshheading:7498322-Dose-Response Relationship, Drug,
pubmed-meshheading:7498322-Humans,
pubmed-meshheading:7498322-Male,
pubmed-meshheading:7498322-Muscle, Smooth, Vascular,
pubmed-meshheading:7498322-Naphthalenes,
pubmed-meshheading:7498322-Rabbits,
pubmed-meshheading:7498322-Rats,
pubmed-meshheading:7498322-Rats, Sprague-Dawley,
pubmed-meshheading:7498322-Thiophenes,
pubmed-meshheading:7498322-Time Factors
|
| pubmed:year |
1995
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| pubmed:articleTitle |
Pharmacology of a potent long-acting imidazole-5-acrylic acid angiotensin AT1 receptor antagonist.
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| pubmed:affiliation |
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
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| pubmed:publicationType |
Journal Article
|