Effects of imidapril therapy on endogenous fibrinolysis in patients with recent myocardial infarction

Soejima, Hirofumi; Ogawa, Hisao; Yasue, Hirofumi; Suefuji, Hisakazu; Kaikita, Koichi; Nishiyama, Koichi

doi:10.1002/clc.4960200507

Cited by 25 publications

(19 citation statements)

References 22 publications

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“…1,8 In Japa- nese patients with myocardial infarction, administration of imidapril (5 mg daily) for 1 month did not change the level of tPA antigen but decreased the level of PAI-1. 28 In summary, the present study demonstrated that ACE inhibition increases constitutive coronary t-PA release without affecting PAI-1 level in women but not in men. The cardiovascular protective effect of ACE-I may be in part related to coronary t-PA release through the augmentation of endogenous BK.…”

Section: Discussionsupporting

confidence: 46%

Angiotensin-Converting Enzyme Inhibition Augments Coronary Release of Tissue Plasminogen Activator in Women But Not in Men

et al. 2010

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Abstract-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 sinusϪaorta gradient of t-PA)ϫ(coronary blood flow)ϫ[(100Ϫhematocrit)/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 (PϽ0.05; man non-ACE-I group: 1.4Ϯ2.6 ng/mL; woman non-ACE-I group: 1.4Ϯ3.1 ng/mL; man ACE-I group: Ϫ1.8Ϯ2.8 ng/mL; woman ACE-I group: 14.8Ϯ3.6 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 (rϭϪ0.38; PϽ0.05) but not in men. ACE inhibition increases coronary release of t-PA in women but not in men. (Hypertension. 2010;56:364-368.)Key Words: angiotensin-converting enzyme inhibitor Ⅲ bradykinin Ⅲ sex Ⅲ tissue plasminogen activator Ⅲ coronary I nhibition of angiotensin-converting enzyme (ACE) has been shown to improve endothelial function, which predicts future cardiovascular events. The renin-angiotensin system and the fibrinolytic system are linked through ACE at the level of the vascular endothelium. 1 Inhibition of ACE favorably alters the fibrinolytic balance by increasing the release of bradykinin (BK)-induced tissue plasminogen activator (t-PA), decreasing the release of angiotensin II-mediated plasminogen activator inhibitor 1 (PAI-1), or both. 1 t-PA is released from the endothelium both constitutively and in response to agonists such as BK and substance P. 2 Exogenous BK stimulates t-PA release from the human forearm vasculature, and chronic ACE inhibition markedly potentiates this effect. 3 Coronary release of t-PA from the endothelium is an important defense against coronary thrombosis. We have shown previously that intracoronary infusion of BK stimulates t-PA release in the human coronary vasculature without affecting plasma PAI-1 level and that ACE inhibition potentiates this effect. 4 Endothelial fibrinolytic capacity, as measured by stimulated t-PA release, has been identified as a novel determinant of future cardiovascular risk. 5 Recently, it has been shown that acute inhibition of ...

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Section: Discussionsupporting

confidence: 46%

Angiotensin-Converting Enzyme Inhibition Augments Coronary Release of Tissue Plasminogen Activator in Women But Not in Men

et al. 2010

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“…Many other studies have demonstrated the beneficial effects of ACE-I on prothrombotic state, [12][13][14][15][16][17] as well as insulin sensitivity [58][59][60] in addition to their efficacy in normalizing elevated BP, which might result in better cardiovascular protection by these drugs. In this regard, a meta-analysis of clinical studies has shown that ACE-I but not ARB may reduce the risk of major coronary disease events.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14][15][16][17] The effects of ACE-Is on t-PA are more controversial, as some studies have shown increased t-PA levels, 18,19 other studies have reported decreased t-PA levels 12,20 and still others have observed unchanged t-PA levels during ACE inhibition. 13,21,22 One possible explanation for these contrasting findings might be that t-PA exists in several forms, including free active t-PA and t-PA bound to PAI-1 and other inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Fibrinolysis and insulin sensitivity in imidapril and candesartan (FISIC study) recipients with hypertension

et al. 2010

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The aim of this study was to evaluate the effects of imidapril and candesartan on fibrinolysis and insulin sensitivity in normoweight hypertensive patients. After a 2-week wash-out period, 61 patients with mild-to-moderate hypertension were randomized to imidapril or candesartan for 12 weeks. Blood pressure (BP), plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen activities were evaluated at baseline and during treatment. The patients underwent a euglycemic-hyperinsulinemic clamp (insulin sensitivity was evaluated as glucose infusion rate during the last 30 min) and a desmopressin test (with desmopressin infusion in the brachial artery) to evaluate endothelial ability to release t-PA. Imidapril and candesartan induced similar systolic/diastolic BP reductions (À16/12.6 and À16.1/12.2 mm Hg, respectively, Po0.001 vs. baseline). Imidapril increased glucose infusion rate (+1.1 mg min À1 per kg, Po0.02), whereas candesartan did not change it. Both drugs decreased PAI-1 antigen activity after 4 weeks of treatment; subsequently, only the decreasing effect of imidapril was sustained throughout the 12 weeks, whereas candesartan increased PAI-1 activity at week 12 (Po0.05 vs. baseline, Po0.01 vs. imidapril). Activity of t-PA decreased with candesartan (from 0.48 ± 0.16 to 0.43 ± 0.14 IU ml À1 , Po0.05) but not with imidapril. Activity of t-PA in response to desmopressin was increased more by imidapril (+4.45 IU ml À1 ) than by candesartan (+2.73 IU ml À1 , Po0.01 vs. imidapril). These results indicate that in normoweight hypertensive patients, despite similar BP reduction, imidapril but not candesartan improved the fibrinolytic balance, suggesting that mechanisms other than Ang II inhibition, possibly including bradykinin-mediated effects on insulin sensitivity and endothelial function, may be responsible for these different effects.

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“…[8][9][10] Blockade of the RAS by angiotensin-converting enzyme inhibitors (ACE-Is) has been generally demonstrated to reduce PAI-1 levels in both experimental and clinical studies. [11][12][13][14][15][16] Contrasting results have been reported about the effects on fibrinolysis of Ang II receptor blockers (ARBs), which inhibit the RAS throughout the block of the effects of Ang II at the AT1 receptor level. [17][18][19][20][21][22] Most studies showed no influence, [17][18][19][20] whereas only a few studies showed a reduction in PAI-1 plasma levels with ARBs.…”

Section: Introductionmentioning

confidence: 99%

Role of angiotensin II in plasma PAI-1 changes induced by imidapril or candesartan in hypertensive patients with metabolic syndrome

et al. 2011

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To evaluate the relationship between plasma plasminogen activator inhibitor-1 (PAI-1) and angiotensin II (Ang II) changes during treatment with imidapril and candesartan in hypertensive patients with metabolic syndrome. A total of 84 hypertensive patients with metabolic syndrome were randomized to imidapril 10 mg or candesartan 16 mg for 16 weeks. At weeks 4 and 8, there was a dose titration to imidapril 20 mg and candesartan 32 mg in nonresponders (systolic blood pressure (SBP) 4140 and/or diastolic blood pressure (DBP) 490 mm Hg). We evaluated, at baseline and after 2, 4, 8, 12 and 16 weeks, clinic blood pressure, Ang II and PAI-1 antigen. Both imidapril and candesartan induced a similar SBP/DBP reduction (À19.4/16.8 and À19.5/16.3 mm Hg, respectively, Po0.001 vs. baseline). Both drugs decreased PAI-1 antigen after 4 weeks of treatment, but only the PAI-1 lowering effect of imidapril was sustained throughout the 16 weeks (À9.3 ng ml À1 , Po0.01 vs. baseline), whereas candesartan increased PAI-1 (+6.5 ng ml À1 , Po0.05 vs. baseline and Po0.01 vs. imidapril). Imidapril significantly decreased Ang II levels (À14.6 pg ml À1 at week 16, Po0.05 vs. baseline), whereas candesartan increased them (+24.2 pg ml À1 , Po0.01 vs. baseline and vs. imidapril). In both groups there was a positive correlation between Ang II and PAI-1 changes (r¼0.61, Po0.001 at week 16 for imidapril, and r¼0.37, Po0.005 at week 16 for candesartan). Imidapril reduced plasma PAI-1 and Ang II levels, whereas candesartan increased them. This suggests that the different effect of angiotensin-converting enzyme inhibitors and Ang II blockers on Ang II production has a role in their different influence on fibrinolysis.

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Effects of imidapril therapy on endogenous fibrinolysis in patients with recent myocardial infarction

Cited by 25 publications

References 22 publications

Angiotensin-Converting Enzyme Inhibition Augments Coronary Release of Tissue Plasminogen Activator in Women But Not in Men

Angiotensin-Converting Enzyme Inhibition Augments Coronary Release of Tissue Plasminogen Activator in Women But Not in Men

Fibrinolysis and insulin sensitivity in imidapril and candesartan (FISIC study) recipients with hypertension

Role of angiotensin II in plasma PAI-1 changes induced by imidapril or candesartan in hypertensive patients with metabolic syndrome

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