Angiotensin-converting enzyme inhibition but not angiotensin II receptor blockade regulates matrix metalloproteinase activity in patients with glomerulonephritis
Details
Serval ID
serval:BIB_66E41448CF49
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Angiotensin-converting enzyme inhibition but not angiotensin II receptor blockade regulates matrix metalloproteinase activity in patients with glomerulonephritis
Journal
Journal of the American Society of Nephrology
ISSN
1046-6673 (Print)
Publication state
Published
Issued date
11/2003
Volume
14
Number
11
Pages
2861-72
Notes
Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't --- Old month value: Nov
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't --- Old month value: Nov
Abstract
Equivalent long-term effects on the kidney are attributed to angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB). Nevertheless, it is unknown to which degree effects of these compounds on individual inflammatory mediators, including matrix metalloproteinases (MMP), are comparable. On the basis of structural and functional differences, it was hypothesized that ACEI and ARB differentially regulate MMP activity. In a randomized, prospective crossover trial, the effect of an ACEI (fosinopril; 20 mg/d) and of an ARB (irbesartan; 150 mg/d) on MMP activity was evaluated. Ten hypertensive patients with glomerulonephritis and normal or mildly reduced creatinine clearance were studied. MMP activity and tissue inhibitors of metalloproteinase (TIMP) levels were analyzed in serum and urine: without therapy, with ACEI, with ARB, and with both agents combined. Treatment periods continued for 6 wk separated by periods of 4 wk each without therapy. Untreated patients with glomerulonephritis displayed distinctively higher serum levels of MMP-2 but much lower MMP-1/-8/-9 concentrations compared with healthy control subjects. Immunohistology of MMP-2 and MMP-9 in kidney biopsy specimen was accordingly. However, these patients excreted higher amounts of MMP-2 and MMP-9 in urine than healthy control subjects, possibly reflecting ongoing glomerular inflammation. In patients with glomerulonephritis, ACEI significantly reduced overall MMP serum activity to 25%, whereas ARB did not show any effect. Activities of MMP-1/-2/-8/-9 were also significantly inhibited by fosinopril but not by irbesartan. Levels of TIMP-1/-2 remained unaffected. In conclusion, ACEI and ARB differentially regulate MMP activity, which may ultimately have consequences in certain types of MMP-dependent glomerulonephritis.
Keywords
Adult
*Angiotensin II Type 1 Receptor Blockers
Angiotensin-Converting Enzyme Inhibitors/*administration & dosage
Biphenyl Compounds/*administration & dosage
Case-Control Studies
Chronic Disease
Cross-Over Studies
Drug Therapy, Combination
Female
Fosinopril/*administration & dosage
Glomerulonephritis/*metabolism
Humans
Male
Matrix Metalloproteinases/drug effects/*metabolism
Middle Aged
Polycystic Kidney, Autosomal Dominant/metabolism
Prospective Studies
Tetrazoles/*administration & dosage
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 14:03
Last modification date
20/08/2019 15:22