Document Detail

Reversal of low dose angiotension hypertension by angiotensin receptor antagonists.
MedLine Citation:
PMID:  1860708     Owner:  NLM     Status:  MEDLINE    
During acute angiotension II (Ang II) infusion (200 ng/kg/min i.v.) into anesthetized rats, mean arterial pressure rose from 124 +/- 1 to 154 +/- 2 mm Hg. The peptidic Ang II antagonist saralasin lowered arterial pressure in a dose-dependent manner. The maximal decrease in pressure was similar to that observed after the Ang II infusion was discontinued. The nonpeptide Ang II antagonist, 4'-[( 2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazole-1-yl] methyl) [1,1'-biphenyl] -2-carboxylic acid (SC-48742), lowered acutely elevated arterial pressure to a level similar to that on discontinuation of the angiotensin infusion. Chronic (8 days) infusion of Ang II (20 ng/kg/min i.v.) increased mean arterial pressure from 116 +/- 3 to 164 +/- 7 mm Hg, which then decreased to 121 +/- 6 mm Hg on termination of the infusion. Saralasin (10 micrograms/kg/min, a maximally effective dose during acute angiotensin infusion) decreased mean arterial pressure from 168 +/- 7 to 141 +/- 3 mm Hg, a pressure significantly higher (p less than 0.05) than the pressure observed after the angiotensin infusion was discontinued. SC-48742 decreased mean arterial pressure from 167 +/- 7 to 127 +/- 3 mm Hg, a pressure not statistically different from the minimum pressure observed after the angiotensin infusion was terminated. The mechanism of blood pressure elevation during acute high dose or chronic low dose Ang II infusion is different, the latter having a significant neural component as measured by the response to trimethaphan. The peptidic antagonist saralasin was fully effective in lowering acute angiotensin hypertension but only partially effective during chronic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
G J Smits; J P Koepke; E H Blaine
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Hypertension     Volume:  18     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1991 Jul 
Date Detail:
Created Date:  1991-09-03     Completed Date:  1991-09-03     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  17-21     Citation Subset:  IM    
Cardiovascular Diseases Research, Searle Research and Development, St. Louis, Mo 63167.
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MeSH Terms
Analysis of Variance
Angiotensin II
Biphenyl Compounds / pharmacology*
Blood Pressure / drug effects
Disease Models, Animal
Dose-Response Relationship, Drug
Hypertension / chemically induced*,  prevention & control
Imidazoles / pharmacology*
Infusions, Intravenous
Rats, Inbred Strains
Receptors, Angiotensin / antagonists & inhibitors*
Saralasin / pharmacology*
Reg. No./Substance:
0/Biphenyl Compounds; 0/Imidazoles; 0/Receptors, Angiotensin; 11128-99-7/Angiotensin II; 114798-27-5/EXP7711; 34273-10-4/Saralasin

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