Linked Life Data

2351436

Source:http://linkedlifedata.com/resource/pubmed/id/2351436

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6 Pt 2
pubmed:dateCreated
1990-7-13
pubmed:abstractText
A series of nonpeptide angiotensin II (Ang II) receptor antagonists was evaluated in rat adrenal cortical microsomes for their inhibitory effects on the specific binding of [3H]Ang II, in the isolated rabbit aorta bioassay for their functional antagonism of contractile response to Ang II, and in high renin, renal-hypertensive rats for their intravenous antihypertensive effects, expressed as IC50, pA2, and intravenous ED30, respectively. Highly significant linear correlations were found between IC50 and pA2 (r = -0.88), between IC50 and intravenous ED30 (r = 0.79), and between pA2 and intravenous ED30 (r = -0.93). In both in vitro and in vivo functional assays, none of these antagonists exhibited agonistic effects. The orally active nonpeptide Ang II receptor antagonists EXP9270 and DuP 753 (oral ED30 = 3.6 and 0.59 mg/kg, respectively) were selected for further characterization. These antagonists exhibited selective and competitive Ang II antagonism in rabbit aorta and guinea pig ileum. In conscious normotensive rats, DuP 753 abolished the pressor response to saralasin, suggesting that the pressor effect of saralasin is attributed to its Ang II-like activity. In addition, DuP 753 also blocked the Ang II-induced drinking response and aldosterone release in rats. These results suggest that Ang II receptor blockade is the primary mechanism of the antihypertensive effect of these nonpeptide Ang II receptor antagonists. Further, the specificity and lack of partial agonistic effects of these molecules make them potentially useful physiological probes and therapeutic agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0194-911X
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
823-34
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Nonpeptide angiotensin II receptor antagonists. Studies with EXP9270 and DuP 753.
pubmed:affiliation
Medical Products Department, E. I. du Pont de Nemours & Company, Wilmington, Delaware 19880-0400.
pubmed:publicationType
Journal Article