title: Effects of the angiotensin receptor blocker candesartan on arterial stiffness and markers of extracellular matrix metabolism in patients with essential hypertension.
abstract: Laboratory studies have shown that angiotensin receptor blockers (ARBs) can affect extracellular matrix (ECM) metabolism and thereby have a beneficial effect on vascular remodeling. The aim of this study was to examine the clinical effects of the ARB candesartan cilexetil on serum markers of synthesis and degradation of ECM, as well as their relation to changes in arterial stiffness in hypertensive patients. Twenty-three patients with essential hypertension were recruited for this study. Markers related to ECM synthesis and degradation (procollagen type 1 propeptide [PIP], procollagen type III propeptide [PIIIP], matrix metalloproteinase-3 [MMP-3, stromelysin-1], tissue inhibitor of matrix metalloproteinases [TIMP-1], and hyaluronic acid [HA]) were examined both before and after one year of treatment with candesartan. Pulse-wave velocity [PWV] and ankle-brachial pressure index [ABI] were measured two months (i.e., after achieving blood pressure reduction) and one year after the initiation of therapy. PWV values after one year of treatment with ARB were significantly decreased compared to previous values, whereas ABI values were unchanged. Treatment with ARB was also associated with a significant decrease in serum PIIIP values and an increase in serum stromelysin-1, whereas changes in PIP, TIMP-1, and HA did not achieve statistical significance. A significant relationship was found between the changes in PWV and the changes in stromelysin-1 levels after correction for blood pressure and heart rate (p = 0.02). These results suggest that the treatment for just one year with ARB results in significant changes in markers of ECM metabolism as well as PWV. These effects on ECM metabolism could have a beneficial effect in decreasing vascular pathology in patients with essential hypertension.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. sasamura@sc.itc.keio.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasamura
authors.forename: Yudai
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Mari
authors.initials: M
authors.lastname: Nakamura
authors.forename: Munekazu
authors.initials: M
authors.lastname: Ryuzaki
authors.forename: Takao
authors.initials: T
authors.lastname: Saruta
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D013777:Tetrazoles / Q000627:therapeutic use*; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D010446:Peptide Fragments; D011347:Procollagen; D013777:Tetrazoles; D019715:Tissue Inhibitor of Metalloproteinase-1; C047202:procollagen Type I N-terminal peptide; C041876:procollagen Type III-N-terminal peptide; D006820:Hyaluronic Acid; D019278:Matrix Metalloproteinase 3; C077793:candesartan cilexetil