Document Detail

Systemic and coronary effects of the angiotensin II receptor antagonist EXP3174 in dogs.
MedLine Citation:
PMID:  7690096     Owner:  NLM     Status:  MEDLINE    
The effects of EXP3174 (0.03-0.3 mg/kg), the active metabolite of the angiotensin II (AII) receptor antagonist losartan, on systemic and coronary hemodynamics as well as on regional myocardial blood flow (radioactive microspheres) were evaluated in anesthetized, open-chest dogs with or without preactivated renin-angiotensin system (RAS) (furosemide treatment). These effects were compared with those of the angiotensin-converting enzyme (ACE) inhibitor enalaprilat (0.1-1 mg/kg). In dogs without preactivated RAS, EXP3174 or enalaprilat did not exert marked hemodynamic effects other did not exert marked hemodynamic effects other than a significant decrease in mean arterial blood pressure (MAP) at the highest doses. In dogs with preactivated RAS, EXP3174 induced a marked, dose-dependent decrease in MAP (maximum decrease -23 +/- 7%), associated with a significant decrease in total peripheral resistance (TPR), whereas cardiac output (CO), heart rate (HR), and left ventricular dP/dt remained unchanged. At the coronary level, EXP3174 induced a decrease in mean coronary resistance that paralleled that of AP. Similar systemic and coronary hemodynamic effects were obtained with enalaprilat administered at doses three times higher. However, regional myocardial tissue perfusion, assessed by the microspheres technique (whether subendocardial, subepicardial, or transmural) or its transmural distribution (endo/epi ratios) was not affected by EXP3174 or enalaprilat. Thus, these results indicate that blockade of the AT1 receptor of AII by EXP3174 induces hemodynamic modifications similar to those evoked by the ACE inhibitor enalaprilat. The lack of effect of EXP3174 or enalaprilat on regional myocardial blood flow (RMBF) suggests, however, that the RAS does not play a role in regulation of myocardial tissue perfusion.
V Richard; A Berdeaux; J F Giudicelli
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  22     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1993 Jul 
Date Detail:
Created Date:  1993-10-07     Completed Date:  1993-10-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  52-7     Citation Subset:  IM    
Département de Pharmacologie, Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre, France.
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MeSH Terms
Angiotensin I / analysis
Angiotensin II / analysis
Coronary Circulation / drug effects*
Enalaprilat / pharmacology
Furosemide / pharmacology
Hemodynamics / drug effects*
Imidazoles / pharmacology*
Receptors, Angiotensin / antagonists & inhibitors*
Renin-Angiotensin System / drug effects
Tetrazoles / pharmacology*
Reg. No./Substance:
0/Imidazoles; 0/Receptors, Angiotensin; 0/Tetrazoles; 11128-99-7/Angiotensin II; 124750-92-1/EXP3174; 54-31-9/Furosemide; 84680-54-6/Enalaprilat; 9041-90-1/Angiotensin I

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