Effect of combined angiotensin-converting enzyme and aldosterone inhibition on plasma plasminogen activator inhibitor type 1 levels in chronic hypertensive patients.
OBJECTIVE
A possible link between the renin-angiotensin-aldosterone system (RAAS) and fibrinolysis has recently been suggested. Systemic infusion of angiotensin II results in an increase in plasminogen activator inhibitor type 1 (PAI-1) levels and angiotensin-converting enzyme inhibitors (ACEI) have been shown to decrease PAI-1 levels. Moreover, recent data indicated that plasma aldosterone levels were positively correlated with plasma PAI-1 levels. This study was designed to compare the effects of an ACEI with an ACEI in combination with an aldosterone antagonist on PAI-1 levels in chronic hypertensive patients.


METHODS
Patients were randomized into two groups and were treated with either low salt diet plus fosinopril (group 1, n = 43) or low salt diet plus fosinopril plus spironolactone (group 2, n = 42). Plasma PAI-1, tissue plasminogen activator (tPA) and plasma renin activity (PRA) levels were measured before and after 24 week treatment in both groups.


RESULTS
The mean basal PRA levels were similar in both groups. After antihypertensive therapy, the mean PRA increased significantly in both groups (P < 0.005). The mean plasma PAI-1 levels were reduced in both treatment groups (P < 0.005). However, the reduction in group 2 was more pronounced (P < 0.05). Although after the treatment mean plasma levels of PAI-1 significantly reduced in both groups, the reduction of PAI-1 levels was more pronounced in group 2.


CONCLUSIONS
Although the plasma levels of PAI-1 significantly reduced after treatment in both groups, the reduction of PAI-1 levels was more pronounced in group 2. These data indicated that administration of aldosterone antagonists in combination with ACEI had additional benefit on fibrinolysis in chronic hypertensive patients.
Tiryaki
Ozlem
O
Department of Nephrology, Gaziantep University School of Medicine, Gaziantep, Turkey. ozlemtir@gmail.com
Usalan
Celalettin
C
Buyukhatipoglu
Hakan
H
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D004039:Diet, Sodium-Restricted; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D017328:Fosinopril / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D012083:Renin / Q000097:blood; D013148:Spironolactone / Q000627:therapeutic use*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D000451:Mineralocorticoid Receptor Antagonists; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D013148:Spironolactone; D010959:Tissue Plasminogen Activator; D012083:Renin; D017328:Fosinopril