Angiotensin-converting enzyme inhibitors : A new mechanism of action

Angiotensin-converting enzyme (ACE) inhibitors are valuable agents for the treatment of hypertension, heart failure, and other cardiovascular and renal diseases. The cardioprotective effects of ACE inhibitors are mediated by blockade of both conversion of angiotensin (Ang) I to Ang II and kinin hydr...

Full description

Saved in:
Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2005-10, Vol.112 (16), p.2436-2445
Main Authors: HONGMEI PENG, CARRETERO, Oscar A, VULJAJ, Nikola, LIAO, Tang-Dong, MOTIVALA, Apurva, PETERSON, Edward L, RHALEB, Nour-Eddine
Format: Article
Language:English
Subjects:
Angiotensin II - pharmacology
Angiotensin-Converting Enzyme Inhibitors - pharmacology
Animals
Biological and medical sciences
Blood and lymphatic vessels
Blood Pressure - drug effects
Captopril - pharmacology
Cardiology. Vascular system
Cardiomegaly - physiopathology
Cardiovascular system
Cell Division - drug effects
Collagen - metabolism
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Heart - drug effects
Hematologic and hematopoietic diseases
Kidney - drug effects
Kidney - metabolism
Leukocyte Count
Male
Medical sciences
Miscellaneous
Myocardium - cytology
Myocardium - metabolism
Pharmacology. Drug treatments
Platelet diseases and coagulopathies
Rats
Rats, Sprague-Dawley
Ventricular Function, Left - drug effects
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Angiotensin-converting enzyme (ACE) inhibitors are valuable agents for the treatment of hypertension, heart failure, and other cardiovascular and renal diseases. The cardioprotective effects of ACE inhibitors are mediated by blockade of both conversion of angiotensin (Ang) I to Ang II and kinin hydrolysis. Here, we report a novel mechanism that may explain the cardiac antifibrotic effect of ACE inhibition, involving blockade of the hydrolysis of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP). To study the role of Ac-SDKP in the therapeutic effects of the ACE inhibitor captopril, we used a model of Ang II-induced hypertension in rats treated with the ACE inhibitor either alone or combined with a blocking monoclonal antibody (mAb) to Ac-SDKP. These hypertensive rats had left ventricular hypertrophy (LVH) as well as increases in cardiac fibrosis, cell proliferation, transforming growth factor-beta (TGF-beta) expression, and phosphorylation of Smad2 (P-Smad2), a signaling mediator of the effects of TGF-beta. The ACE inhibitor did not decrease either blood pressure or LVH; however, it significantly decreased LV collagen from 13.3+/-0.9 to 9.6+/-0.6 microg/mg dry wt (P
ISSN:0009-7322
1524-4539
DOI:10.1161/CIRCULATIONAHA.104.528695