Angiotensin-converting enzyme inhibition but not angiotensin II type 1 receptor antagonism augments coronary release of tissue plasminogen activator in hypertensive patients.
OBJECTIVE
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 microg/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.
Matsumoto
Tetsuya
T
First Department of Internal Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Japan. tetsuyam@belle.shiga-med.ac.jp
Minai
Kazuo
K
Horie
Hajime
H
Ohira
Naoto
N
Takashima
Hiroyuki
H
Tarutani
Yasuhiro
Y
Yasuda
Yo
Y
Ozawa
Tomoya
T
Matsuo
Shinro
S
Kinoshita
Masahiko
M
Horie
Minoru
M
D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001920:Bradykinin / Q000378:metabolism*; D003326:Coronary Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000008:administration & dosage / Q000494:pharmacology*; D044140:Receptor, Angiotensin, Type 1; D010959:Tissue Plasminogen Activator / Q000097:blood*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D010959:Tissue Plasminogen Activator; D019808:Losartan; D001920:Bradykinin; D020913:Perindopril