Plasma levels of active extracellular matrix metalloproteinases 2 and 9 in patients with essential hypertension before and after antihypertensive treatment.
This study was designed to test the hypothesis that plasma concentrations of matrix metallo-proteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two enzymes that share similar substrate specificity (collagen type IV and V), possibly related to vascular remodelling, are altered in essential hypertension. The second aim of the study was to assess whether chronic antihypertensive treatment with the calcium channel blocker amlodipine would normalize these alterations. To test this hypothesis, we measured plasma concentrations of active MMP-2 and MMP-9 in 42 patients with never-treated essential hypertension and in 25 normotensive control subjects. Measurements were repeated after 6 months of treatment with the calcium channel blocker amlodipine. Baseline values of MMP-2 and MMP-9 were decreased (P=0.01 and 0.002, respectively) in hypertensive patients compared with normotensives. Hypertensive patients with systemic vascular resistances <1440 dyn s/cm(5) exhibited higher values of MMP-2 (P=0.005) and MMP-9 (P=0.001) than hypertensive patients with systemic vascular resistances >1440 dyn s/cm(5). Treated patients attained a nonsignificant increase in MMP-2 plasma concentrations, but a significant increase in MMP-9 plasma concentrations (P=0.01) compared to respective values before treatment. In conclusion, these findings suggest that plasma concentrations of active MMP-2 and MMP-9, mainly related to vascular extracellular matrix metabolism, are depressed in patients with essential hypertension. A 6 month treatment with amlodipine can normalize MMP-9 but not MMP-2 plasma concentrations. The hypothesis that antihypertensive treatment may modulate collagen metabolism remains to be determined by further studies.
Zervoudaki
A
A
Department of Cardiology, Athens University, Hippokratio Hospital, 3 Athanasiou Diakou Str., GR-151 22, Marousi, Athens, Greece. fotvlast@otenet.gr
Economou
E
E
Stefanadis
C
C
Pitsavos
C
C
Tsioufis
K
K
Aggeli
C
C
Vasiliadou
K
K
Toutouza
M
M
Toutouzas
P
P
D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood* / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000187:drug effects*; D008875:Middle Aged; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D017311:Amlodipine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9