Document Detail


Mechanism of action of enalapril in experimental hypertension and acute left ventricular failure.
MedLine Citation:
PMID:  6100609     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mechanism of action of angiotensin converting enzyme (ACE) inhibitors to lower blood pressure remains unclear, but the weight of available data favour peripheral blockade of the formation of angiotensin II (AII). Previous work in rats has shown that the prodrug ACE inhibitor, enalapril (MK-421), lowered blood pressure most effectively when PRA was elevated [sodium deficiency, two-kidney, one figure 8 hypertension, diuretic-treated spontaneously hypertensive rats (SHR)]. In sodium-deficient rats, the enalapril-sensitive component of the blood pressure was greatly reduced after salt loading, and nephrectomy blocked the antihypertensive response to enalapril in SHR. In the present study, further support that the mechanism of action of enalapril involves a reduction in AII has been obtained from rats made hypertensive by continuous intravenous (i.v.) AII infusion for 10 days. Enalapril administered for seven days did not significantly lower blood pressure, suggesting that there were no important non-angiotensin mechanisms (such as bradykinin potentiation) involved in its action. From earlier studies in SHR, the time course for blockade of angiotensin I (AI) pressor responses and the blood pressure reduction did not correspond, suggesting a tissue site of action. In the present studies in adult SHR, a central site of action was ruled out since the parent inhibitor, enalaprilic acid (MK-422), injected into the brain ventricles did not acutely reduce blood pressure. An interaction of enalaprilic acid with the sympathetic nervous system was evaluated in dogs in which adrenergic activity was enhanced as a result of diuretic-induced renin release. Enlaprilic acid did not alter the enhanced hindquarter vasoconstrictor responses to sympathetic nerve stimulation. Enalapril increased renal blood flow, glomerular filtration rate and sodium excretion. The mechanism of the natriuresis in dogs probably involves several mechanisms including a decrease in aldosterone biosynthesis, changes in renal function (glomerular filtration rate and renal blood flow) and possibly blockade of a direct tubular effect of AII on sodium reabsorption. Enalaprlic acid was also studied in a closed chest dog model of acute left ventricular (LV) failure caused by embolization via the left main coronary artery with 50 microns plastic microspheres. Enalaprilic acid at 100 micrograms/kg i.v. reduced preload, afterload and improved LV performance without changing the heart rate. In conclusion, enalapril the prodrug, and enalaprilic acid the active inhibitor, are potentially useful in the treatment of hypertension and LV failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
C S Sweet; S L Gaul; P M Reitz; E H Blaine; L T Ribeiro
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of hypertension. Supplement : official journal of the International Society of Hypertension     Volume:  1     ISSN:  0952-1178     ISO Abbreviation:  J Hypertens Suppl     Publication Date:  1983 Oct 
Date Detail:
Created Date:  1986-02-18     Completed Date:  1986-02-18     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8501422     Medline TA:  J Hypertens Suppl     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  53-63     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adrenalectomy
Angiotensin II / pharmacology*
Animals
Blood Pressure / drug effects*
Captopril / pharmacology
Dogs
Enalapril / pharmacology*
Female
Heart Failure / physiopathology*
Heart Ventricles / drug effects,  physiopathology
Hindlimb
Hypertension / physiopathology*
Hypertension, Renal / physiopathology
Kidney / physiology
Male
Muscles / blood supply
Rats
Rats, Inbred SHR
Renin / blood
Sodium / metabolism
Vasoconstriction / drug effects
Chemical
Reg. No./Substance:
11128-99-7/Angiotensin II; 62571-86-2/Captopril; 7440-23-5/Sodium; 75847-73-3/Enalapril; EC 3.4.23.15/Renin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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