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(Hypertension. 1998;31:321.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Relationship Between Endothelial Function and Fibrinolysis in Early Hypertension

Hirofumi Tomiyama; Yutaka Kimura; Hiroyuki Mitsuhashi; Takashi Kinouchi; Hideo Yoshida; Toshio Kushiro; Nobutaka Doba

From the Division of Cardiology (H.T., H.Y.,N.D.) and Laboratory Medicine (Y.K., H.M., T.K.), The Third Department of Internal Medicine, Teikyo University School of Medicine, Ichihara Hospital, Ichihara, Chiba, Japan and the Department of Cardiology (T.K.), Surugadai Nihon University Hospital

Correspondence to Hirofumi Tomiyama, MD, Division of Cardiology, The Third Department of Internal Medicine, Teikyo University School of Medicine, Ichihara Hospital, 3426-3, Anegasaki, Icihara, Chiba, Japan. 299-01. E-mail h-tomiya{at}med.teikyo-u.ac.jp

Abnormalities in fibrinolysis, endothelial function, and glucose and lipid metabolism have been reported in hypertension. This study was conducted to examine the interrelationships between fibrinolytic factors, glucose and lipid metabolism, and endothelial function in hypertension. The effects of administering an angiotensin converting enzyme inhibitor, benazepril, were also examined. Blood levels of the following substances were measured in patients with borderline and mild hypertension (n=50, 51±19 years) and in age-matched controls (n=10): total cholesterol, triglycerides, tissue plasminogen activator activity and antigen, and plasminogen activator inhibitor type 1 activity and antigen. Insulin sensitivity was assessed by oral glucose tolerance test, and endothelial function was assessed by evaluating changes in diameter of the brachial artery during reactive hyperemia as observed by ultrasonography. Activities of tissue plasminogen activator and plasminogen activator inhibitor type 1 were both elevated in the hypertensive patients. Stepwise multiple regression analysis showed that plasminogen activator inhibitor type 1 antigen correlated with insulin sensitivity, total cholesterol levels, and triglycerides levels (P<.01). Endothelial function was negatively correlated with tissue plasminogen activator activity and antigen (P<.01). The chronic administration of benazepril (5–10 mg/d) for 20 weeks improved insulin sensitivity, endothelial function (6.6+3.49.0+2.5%, P<.01), and tissue plasminogen activator activity and antigen. These results indicate that abnormalities in fibrinolysis are associated with endothelial dysfunction as well as disorders of glucose and lipid metabolism in patients with borderline and mild hypertension. The treatment of such patients with benazepril appeared to improve the impairment in fibrinolysis and endothelial dysfunction.

Key Words: fibrinolysis • endothelium • hypertension • insulin resistance • tissue plasminogen activator • plasminogen activator inhibitor type 1 • angiotensin converting enzyme inhibitor

Abbreviations: ACE = Angiotensin converting enzyme • FDP = fibrinogen/fibrin degradation products • PAI-1 act = plasminogen activator inhibitor type 1 activity • PAI-1 ang = plasminogen activator inhibitor type 1 antigen • PAI-1/tPA = ratio of tPA ang to PAI-1 ang • BS = sigma plasma glucose • INS = sigma plasma insulin • tPA act = tissue plasminogen activator activity • tPA ang = tissue plasminogen activator antigen

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