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CLINICAL STUDY: SYSTEMIC AND PULMONARY HYPERTENSION

Angiotensin-converting enzyme inhibition but not angiotensin II type 1 receptor antagonism augments coronary release of tissue plasminogen activator in hypertensive patients

^* First Department of Internal Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Shiga, Japan

Manuscript received March 5, 2002; revised manuscript received December 27, 2002, accepted January 16, 2003.

^* Reprint requests and correspondence: Dr. Tetsuya Matsumoto, First Department of Internal Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Shiga 520-2192, Japan.
tetsuyam{at}belle.shiga-med.ac.jp

OBJECTIVES: We compared the effects of perindopril and losartan on endothelium-dependent coronary vasomotor and fibrinolytic function.

BACKGROUND: The renin-angiotensin system regulates the vascular fibrinolytic balance. However, the effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists on coronary fibrinolytic function have not been compared in hypertensive patients.

METHODS: Forty-five patients with hypertension were randomly assigned to three groups: 16 patients were treated with perindopril (4 mg/day) for four weeks; 15 were treated with losartan (50 mg/day) for four weeks; and 14 were not treated with either perindopril or losartan (control group). Graded doses of bradykinin (BK) (0.2, 0.6, and 2.0 µg/min) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flow velocity measurement.

RESULTS: Bradykinin induced dose-dependent increases in CBF in all groups. The increases in CBF induced by BK in the perindopril and losartan groups were significantly greater than those in the control group. Net coronary tissue-type plasminogen activator (t-PA) release was enhanced by BK in all groups, and the increase in the perindopril group was greater than that in the losartan and control groups. Bradykinin did not alter plasminogen activator inhibitor type 1 levels in any of the groups.

CONCLUSIONS: Perindopril and losartan similarly augment BK-induced coronary vasodilation. Perindopril may have a greater potential to enhance the BK-induced coronary release of t-PA than losartan.

Abbreviations and Acronyms   ACE   angiotensin-converting enzyme   Ao   aorta   AT1   angiotensin II type 1   BK   bradykinin   CBF   coronary blood flow   CS   coronary sinus   CVR   coronary vascular resistance   HF   heart failure   MAP   mean arterial pressure   NO   nitric oxide   t-PA   tissue-type plasminogen activator   PAI-1   plasminogen activator inhibitor type 1

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