Angiotensin-converting enzyme inhibition augments coronary release of tissue plasminogen activator in women but not in men.
The renin-angiotensin system regulates the vascular fibrinolytic balance. In the human forearm vasculature, angiotensin-converting enzyme (ACE) inhibitors (ACE-Is) increase the release of t-PA through endogenous bradykinin. We tested the hypothesis that ACE inhibition and sex modulate the endogenous coronary release of tissue plasminogen activator (t-PA) in hypertensive patients. Seventy-three patients underwent diagnostic coronary angiography and had normal coronary angiograms. Thirty-three patients (21 men and 12 women) were treated with imidapril (5 mg/day) for 4 weeks (ACE-I group), and 40 (23 men and 17 women) were not treated with ACE-I (non-ACE-I group). All of the women were postmenopausal. Coronary blood flow in the left anterior descending artery was evaluated by measuring Doppler flow velocity. Net coronary t-PA release was determined as (coronary sinus-aorta gradient of t-PA)x(coronary blood flow)x[(100-hematocrit)/100]. Age, arterial pressure, heart rate, lipid levels, coronary flow, and the plasma level of t-PA at either aorta or coronary sinus were comparable among the 4 groups. In women, net t-PA release in the ACE-I group was significantly higher than that in the other groups (P<0.05; man non-ACE-I group: 1.4+/-2.6 ng/mL; woman non-ACE-I group: 1.4+/-3.1 ng/mL; man ACE-I group: -1.8+/-2.8 ng/mL; woman ACE-I group: 14.8+/-3.6 ng/mL). Correction for smoking status gave similar results. There was a significant negative correlation between serum ACE activity and coronary t-PA release in women (r=-0.38; P<0.05) but not in men. ACE inhibition increases coronary release of t-PA in women but not in men.
Matsumoto
Tetsuya
T
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Shiga 520-2192, Japan. tetsuyam@belle.shiga-med.ac.jp
Takashima
Hiroyuki
H
Nakae
Ichiro
I
Yamane
Tetsunobu
T
Hayashi
Hideki
H
Horie
Minoru
M
D000368:Aged; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D048289:Imidazolidines / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D012737:Sex Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D048289:Imidazolidines; C065166:imidapril; D007703:Peptidyl-Dipeptidase A; D010959:Tissue Plasminogen Activator