D96 Effects of captopril on fibrinolytic function in healthy humans

Lottermoser, Katja

doi:10.1016/s0895-7061(97)89125-x

Cited by 13 publications

(13 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A similar effect of ACE inhibition on PAI-1 has been observed in at least 6 studies, [15][16][17][18]20,31 but not in others. [32][33][34][35][36] With respect to the effect of ACE inhibition on fibrinolytic balance, one explanation for the conflicting findings is that studies have differed widely in design. The effect of ACE inhibition on fibrinolytic balance may depend on the ACE inhibitor used, the population studied (eg, post-MI, hypertensive, or normotensive), and the state of activation of the RAAS.…”

Section: Discussionmentioning

confidence: 99%

“…The effect of ACE inhibition on tPA is even more controversial than the effect of ACE inhibition on PAI-1, with studies reporting increased, 47 decreased, 17,31,34 and unchanged 15,16,20,32,33,35,36 tPA antigen during ACE inhibition. This controversy stems, in part, from the fact that tPA exists in several forms in blood, including free active tPA and tPA bound to PAI-1 and other inhibitors.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Antagonism on Plasma Fibrinolytic Balance in Humans

1999

View full text Add to dashboard Cite

Abstract-Angiotensin-converting enzyme (ACE) inhibition significantly decreases plasminogen activator inhibitor-1 (PAI-1) without altering tissue plasminogen activator (tPA) during activation of the renin-angiotensin-aldosterone system in humans. Because ACE inhibitors and angiotensin II type 1 (AT 1 ) receptor antagonists differ in their effects on angiotensin II formation and bradykinin degradation, the present study compared the effect of equivalent hypotensive doses of an ACE inhibitor and AT 1 antagonist on fibrinolytic balance. Plasma PAI-1 antigen, tPA antigen, plasma renin activity, and aldosterone were measured in 25 normotensive subjects (19 white, 6 black; 14 men, 11 women; mean age 38.5Ϯ1.8 years; mean body mass index 25.3Ϯ0.7 kg/m 2 ) during low salt intake alone (10 mmol Na/d), low salt intake ϩ quinapril (40 mg PO bid), and low salt intake ϩ losartan (50 mg PO bid). Compared with low salt alone (systolic blood pressure [BP] 118.8Ϯ2.2 mm Hg), both quinapril (106.3Ϯ2.5 mm Hg, PϽ0.001) and losartan (105.4Ϯ2.8 mm Hg, PϽ0.001) reduced BP. No statistical difference was found between quinapril and losartan in their BP lowering effect. Losartan (Pϭ0.009), but not quinapril, lowered heart rate. Both drugs significantly lowered aldosterone (PϽ0.001 versus low salt alone for each); however, this effect was significantly greater for quinapril than for losartan (PϽ0.001 for quinapril versus losartan). Treatment with quinapril, but not with losartan, was associated with a decrease in both PAI-1 antigen (Pϭ0.03) and activity (Pϭ0.018). PAI-1 activity was lower during treatment with quinapril than with losartan (Pϭ0.015). The average PAI-1 antigen concentration was 13.0Ϯ2.0 ng/mL during low salt alone, 10.5Ϯ1.6 ng/mL during quinapril treatment, and 12.3Ϯ2.1 ng/mL during losartan treatment. In contrast, plasma tPA antigen concentrations were reduced during treatment with losartan (Pϭ0.03) but not with quinapril. This study provides the first evidence that ACE inhibitors and AT 1 antagonists differ in their effects on fibrinolytic balance under conditions of activation of the renin-angiotensin-aldosterone system. Further studies are needed to address the mechanism for the contrasting effects of these 2 classes of drugs on fibrinolysis and to define the clinical significance of these differences. (Hypertension. 1999;34:285-290.) Key Words: angiotensin II Ⅲ renin Ⅲ plasminogen activators A ctivation of the renin-angiotensin-aldosterone system (RAAS) has been associated with an increased risk of ischemic cardiovascular events independent of effects on blood pressure (BP). 1,2 Conversely, interruption of the RAAS with an angiotensin-converting enzyme (ACE) inhibitor decreases progression of atherosclerosis in animal models 3,4 and appears to reduce the risk of recurrent myocardial infarction (MI) in patients with left ventricular dysfunction. 5,6 The mechanisms through which activation of the RAAS increases or ACE inhibition decreases the risk of ischemic cardiovascular events in selected populations is not known. One...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparative Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Antagonism on Plasma Fibrinolytic Balance in Humans

1999

View full text Add to dashboard Cite

show abstract

“…For example, ACE inhibitors have been found to reduce PAI-1 antigen concentrations in many, 5,26 -30 but not all, studies. 31,32 The present data suggest that the effect of ACE inhibition on PAI-1 antigen concentrations and fibrinolytic balance may depend on the PAI-1 4G/5G genotype frequencies in the population studied. On the basis of the finding that salt depletion caused the greatest increase in PAI-1 antigen in 4G/4G subjects, the effect of ACE inhibition on circulating PAI-1 antigen would be expected to be greatest in individuals homozygous for the 4G allele.…”

Section: Discussionmentioning

confidence: 61%

Interactive Effect of PAI-1 4G/5G Genotype and Salt Intake on PAI-1 Antigen

Brown

Murphey²,

Srikuma³

et al. 2001

ATVB

View full text Add to dashboard Cite

Abstract-Activation of the renin-angiotensin-aldosterone system (RAAS) is associated with increased circulating PAI-1 antigen and increased risk of thrombotic cardiovascular events. A 4G/5G polymorphism located 675 bp upstream from the transcription start site of the PAI-1 gene affects PAI-1 antigen concentrations. To test the hypothesis that PAI-1 4G/5G genotype influences the effect of activation of the RAAS on PAI-1 expression, we measured morning PAI-1 antigen concentrations in 76 subjects with essential hypertension during low (10 mmol/d) and high (200 mmol/d) salt intake. Low salt intake was associated with activation of the RAAS as measured by plasma renin activity (2.3Ϯ0.2 versus 0.5Ϯ0.0 ng angiotensin I · mL Ϫ1 · h Ϫ1 , PϽ0.001) and aldosterone (529Ϯ40 versus 145Ϯ12 pmol/L). PAI-1 antigen concentrations were 17.9Ϯ2.7, 19.2Ϯ2.5, and 27.8Ϯ4.0 ng/mL during high salt intake and 19.2Ϯ2.7, 21.6Ϯ2.9, and 38.9Ϯ7.2 ng/mL during low salt intake in the 5G/5G (nϭ14), 4G/5G (nϭ40), and 4G/4G (nϭ22) groups, respectively. There was a significant effect of both salt intake (Fϭ6.0, Pϭ0.017) and PAI-1 4G/5G genotype (Fϭ7.6, Pϭ0.001) on PAI-1 antigen. More importantly, there was a significant interactive effect (Fϭ7.8, Pϭ0.001) of salt intake and PAI-1 4G/5G genotype on PAI-1 antigen. PAI-1 4G/5G genotype influenced the relationship between serum triglycerides and PAI-1 antigen such that the relationship was significant only in 4G homozygotes during either high (R 2 ϭ0.31, Pϭ0.014) or low (R 2 ϭ0.37, Pϭ0.006) salt intake. This study identifies an important gene-by-environment interaction that may influence cardiovascular morbidity and the response to pharmacological therapies that interrupt the RAAS. Key Words: thrombosis Ⅲ genetics Ⅲ fibrinolysis Ⅲ coagulation A ctivation of the renin-angiotensin-aldosterone (RAAS) system has been associated with an increased risk of myocardial infarction (MI) and stroke in patients with essential hypertension. 1,2 Conversely, interruption of the RAAS by ACE inhibition reduces the risk of MI in patients at risk for coronary artery disease. 3 Recent studies suggest that the effects of activation and interruption of the RAAS on cardiovascular morbidity and mortality derive in part from an interaction of the RAAS and fibrinolytic systems. 4,5 Endogenous fibrinolysis plays a critical role in limiting thrombosis and depends on the balance between plasminogen activators (primarily tissue plasminogen activator, tPA) and plasminogen activator inhibitors (PAI, predominantly PAI-1). 6,7 Both of these essential fibrinolytic components are synthesized locally in the vascular wall (in endothelial and smooth muscle cells), have short half-lives, and circulate in trace concentrations in the plasma. Increased PAI-1 expression has been demonstrated in atherosclerotic lesions. 8,9 Elevated PAI-1 concentrations are seen in youthful survivors of acute MI compared with age-matched control subjects, 10 and elevated levels of PAI-1 appear to be a risk factor for recurrent MI. 11 PAI-1 antigen and activity are ...

show abstract

“…[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

View full text Add to dashboard Cite

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.

show abstract

D96 Effects of captopril on fibrinolytic function in healthy humans

Cited by 13 publications

References 0 publications

Comparative Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Antagonism on Plasma Fibrinolytic Balance in Humans

Comparative Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Antagonism on Plasma Fibrinolytic Balance in Humans

Interactive Effect of PAI-1 4G/5G Genotype and Salt Intake on PAI-1 Antigen

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

Contact Info

Product

Resources

About