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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:dateCreated |
1998-7-17
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| pubmed:abstractText |
The effects of a nonpeptide, orally active mixed endothelin (ET) ETA/ETB receptor antagonist, SB 217242, and an angiotensin-converting enzyme (ACE) inhibitor, ramipril, were evaluated after inter-renal aortic banding in the rat. Separate sham, vehicle, and treatment groups were compared in each study. In vehicle-treated animals in the ramipril group, aortic banding for 4 weeks produced significant cardiac hypertrophy (247 +/- 5 mg/100 g bw vs. 305 +/- 11 mg/100 g bw; p < 0.001), right (upstream) renal hypertrophy (380 +/- 6 mg/100 g bw vs. 559 +/- 28 mg/100 g bw; p < 0.001), and significant left (downstream) renal atrophy (405 +/- 4 mg/100 g bw vs. 192 +/- 25 mg/100 g bw; p < 0.001). Continuous ramipril treatment (1 mg/kg p.o. once daily), begun 3 days before aortic banding, inhibited cardiac hypertrophy (305 +/- 11 mg/100 g bw vs. 266 +/- 7 mg/100 g bw; p < 0.05) but did not alter renal hypertrophy or atrophy. In a similarly designed study, SB 217242 (30 mg/kg p.o. b.i.d.) had no effect on the development of cardiac hypertrophy (298 +/- 7 mg/100 g bw vs. 310 +/- 12 mg/100 g bw) or renal hypertrophy (561 +/- 15 mg/100 g bw vs. 575 +/- 19 mg/100 g bw), but abolished the development of renal atrophy (158 +/- 16 mg/100 g bw vs. 395 +/- 19 mg/100 g bw; p < 0.001). [125I]ET-1 radioligand binding experiments indicated that the density of both ETA and ETB receptors was increased dramatically (three- to fourfold) in the atrophic kidney cortex compared to sham or hypertrophic kidneys. In situ hybridization studies indicate an upregulation of ETB receptor mRNA in the glomeruli of atrophic kidneys within 5 days of aortic banding. In conclusion, an angiotensin-dependent mechanism may mediate cardiac hypertrophy associated with aortic banding, whereas ET-dependent mechanisms may mediate an atrophic response in the hypoperfused kidney, perhaps through an interaction with upregulated ETA and/or ETB receptors.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin-Converting Enzyme...,
http://linkedlifedata.com/resource/pubmed/chemical/Ramipril,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Endothelin A,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Endothelin B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Endothelin
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| pubmed:status |
MEDLINE
|
| pubmed:issn |
0160-2446
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
31 Suppl 1
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
S277-83
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| pubmed:dateRevised |
2004-1-20
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| pubmed:meshHeading |
pubmed-meshheading:9595459-Angiotensin-Converting Enzyme Inhibitors,
pubmed-meshheading:9595459-Animals,
pubmed-meshheading:9595459-Cardiomegaly,
pubmed-meshheading:9595459-Hypertrophy,
pubmed-meshheading:9595459-In Situ Hybridization,
pubmed-meshheading:9595459-Kidney,
pubmed-meshheading:9595459-Kidney Cortex,
pubmed-meshheading:9595459-Male,
pubmed-meshheading:9595459-Radioligand Assay,
pubmed-meshheading:9595459-Ramipril,
pubmed-meshheading:9595459-Rats,
pubmed-meshheading:9595459-Rats, Sprague-Dawley,
pubmed-meshheading:9595459-Receptor, Endothelin A,
pubmed-meshheading:9595459-Receptor, Endothelin B,
pubmed-meshheading:9595459-Receptors, Endothelin
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| pubmed:year |
1998
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| pubmed:articleTitle |
Effects of endothelin receptor antagonism and angiotensin-converting enzyme inhibition on cardiac and renal remodeling in the rat.
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| pubmed:affiliation |
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceutics, King of Prussia, PA 19406, USA.
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| pubmed:publicationType |
Journal Article
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