Angiotensin-converting enzyme inhibition and smoking potentiate the kinin response to cardiopulmonary bypass

Pretorius, Mias; McFarlane, Julie A.; Vaughan, Douglas E.; Brown, Nancy J.; Murphey, Laine J.

doi:10.1016/j.clpt.2004.06.004

Cited by 10 publications

(13 citation statements)

References 25 publications

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“…[1, 31, 47] Prior studies have indicated that ACE inhibition enhances the bradykinin response during CPB. [48] Moreover, bradykinin increases oxidative stress and worsens ischemia/reperfusion renal injury in an animal model. [49] Thus, ACE inhibition, through an increase in bradykinin concentrations, could increase oxidative stress and contribute to AKI.…”

Section: Discussionmentioning

confidence: 99%

Postoperative acute kidney injury is associated with hemoglobinemia and an enhanced oxidative stress response

Billings¹,

Ball²,

Roberts³

et al. 2011

Free Radical Biology and Medicine

134

129

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Acute kidney injury (AKI) frequently afflicts patients undergoing cardiopulmonary bypass (CPB) and independently predicts death. Both hemoglobinemia and myoglobinemia are independent predictors of postoperative AKI. Release of free hemeproteins into the circulation is known to cause oxidative injury to the kidneys. This study tested the hypothesis that postoperative AKI is associated with both enhanced intraoperative hemeprotein release and increased lipid peroxidation assessed by measuring F 2 -isoprostanes and isofurans. In a case-control study, nested within an ongoing randomized trial of perioperative statin treatment and AKI, we compared levels of F 2 -isoprostanes and isofurans with plasma levels of free hemoglobin and myoglobin in 10 cardiac surgery AKI patients to 10 risk-matched controls. Peak plasma free hemoglobin concentrations were significantly higher in AKI subjects (289.0±37.8 versus 104.4±36.5 mg/dl, P=0.01), whereas plasma myoglobin concentrations were similar between groups. The change in plasma F 2 -isoprostane and isofuran levels (repeated measures ANOVA P=0.02 and P=0.001, respectively) as well as the change in urine isofuran levels (P=0.04) was significantly greater in AKI subjects. In addition, change in peak plasma isofurans levels correlated not only with peak free plasma hemoglobin concentrations (r 2 =0.39, P=0.001) but also with peak change in serum creatinine (r 2 =0.20, P=0.01). Postoperative AKI is associated with both enhanced intraoperative hemeprotein release and enhanced lipid peroxidation. The correlations among hemoglobinemia, lipid peroxidation, and AKI indicate a potential role of hemeprotein-induced oxidative damage in the pathogenesis of postoperative AKI. KeywordsAcute kidney injury; oxidative stress; isoprostanes; isofurans; hemeprotein; cardiac surgery; cardiopulmonary bypass; NGAL Acute kidney injury (AKI) complicates the postoperative course in up to 30% of all cardiac surgery patients and independently predicts in-hospital mortality, morbidity, and mid-term and long-term survival. [1][2][3] Renal hypoperfusion, use of cardiopulmonary bypass (CPB), © 2010 Elsevier Inc. All rights reserved.Correspondence: Mias Pretorius, MBChB, MSCI, 561 PRB, Vanderbilt University Medical Center, Nashville, TN 37232, Fax: (615) 343-2551, Phone: (615) 343-0665, mias.pretorius@vanderbilt.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Clinical Trial Registration Methods Study PopulationData were obtained from participants in the ongoing "The effect of atorvastatin on Acute Kidney Injury following cardiac surgery" (Statin AKI) study...

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Section: Discussionmentioning

confidence: 99%

Postoperative acute kidney injury is associated with hemoglobinemia and an enhanced oxidative stress response

Billings¹,

Ball²,

Roberts³

et al. 2011

Free Radical Biology and Medicine

134

129

View full text Add to dashboard Cite

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“…The concentration of BK1-5 achieved during intra-arterial administration that resulted in maximal platelet inhibition was approximately 50-to 75-fold higher than physiological concentrations Pretorius et al, 2004) but 150,000-fold lower than the concentrations required to inhibit platelet aggregation or in vitro (Hasan et al, 1996(Hasan et al, , 1999 or in vivo in dogs. Species differences may account for the difference in the potency of BK1-5 in dogs and humans.…”

mentioning

confidence: 99%

Bradykinin and Its Metabolite Bradykinin 1-5 Inhibit Thrombin-Induced Platelet Aggregation in Humans

Murphey

Malave

Petro

et al. 2006

J Pharmacol Exp Ther

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Bradykinin 1-5 is a major stable metabolite of bradykinin, formed by the proteolytic action of angiotensin-converting enzyme. In vitro and animal studies suggest that bradykinin 1-5 possesses biological activity. This study tests the hypothesis that bradykinin 1-5 affects vasodilation, fibrinolysis, or platelet aggregation in humans. Graded doses of bradykinin (47-377 pmol/min) and bradykinin 1-5 (47-18,850 pmol/min) were infused in the brachial artery in random order in 36 healthy subjects. Forearm blood flow (FBF) was measured, and simultaneously obtained venous and arterial plasma samples were analyzed for tissue plasminogen activator (t-PA) antigen. In seven subjects each, ␣-and ␥-thrombin-induced platelet aggregation was measured in platelet-rich plasma obtained from antecubital venous blood at baseline and during peptide infusions. Bradykinin caused dose-dependent increases in FBF and net t-PA release (P Ͻ 0.001 for both). Bradykinin 1-5 did not affect FBF (P ϭ 0.13) or net t-PA release (P ϭ 0.46) at concentrations Ͼ1500 times physiologic. In contrast, both bradykinin and bradykinin 1-5 inhibited ␣-and ␥-thrombin-induced platelet aggregation (P Ͻ 0.01 versus baseline). Bradykinin 1-5 inhibited ␥-thrombin-induced platelet aggregation 50% at a calculated dose of 183 Ϯ 3 pmol/min. Neither bradykinin nor bradykinin 1-5 affected thrombin receptor-activating peptideinduced platelet aggregation, consistent with the hypothesis that bradykinin and bradykinin 1-5 inhibit thrombin-induced platelet aggregation by preventing cleavage of the thrombin receptor and liberation of thrombin receptor-activating peptide. This study is the first to demonstrate biological activity of bradykinin 1-5 following in vivo administration to humans. By inhibiting thrombin-induced platelet aggregation without causing vasodilation, bradykinin 1-5 may provide a model for small molecule substrate-selective thrombin inhibitors.Bradykinin (BK) is a vasoactive peptide that exhibits cardioprotective effects. Bradykinin promotes vasodilation (Vanhoutte, 1989), exerts antiproliferative effects (Linz and Scholkens, 1992), inhibits thrombin-induced platelet activation (TRAP) in vitro (Hasan et al., 1996), stimulates endothelial tissue plasminogen activator (t-PA) release (Smith et al., 1985), and contributes to many of the effects of angiotensin-converting enzyme (ACE) inhibition (Gainer et al., 1998;Labinjoh et al., 2001;Minai et al., 2001). Bradykinin stimulates t-PA release from the human forearm vasculature in a dose-dependent manner through a bradykinin B 2 receptordependent pathway (Brown et al., 2000). Systemic bradykinin is rapidly metabolized via ACE in humans to BK1-5 (Murphey et al., 2000a). The identification of BK1-5 as the major stable metabolite of systemic bradykinin in humans raises the question of whether this peptide itself exhibits biological activity, just as studies have demonstrated that degradation products of angiotensin II, once thought to be inactive, have biological activity (Kerins et al., 1995;Brosnihan et al...

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“…Whether or not bradykinin produces detrimental effects may depend on the underlying activity of the kallikrein–kinin system. During CPB, the kallikrein–kinin system is activated 6 , 7 and increased bradykinin may cause detrimental effects such as enhanced stimulation of t‐PA release, with resulting fibrinolysis and bleeding. The endothelium is the principal site of t‐PA synthesis and storage, whereas PAI‐1 is synthesized and secreted from several sources including endothelium, adipose tissue, liver, and platelets 22 , 23 .…”

Section: Discussionmentioning

confidence: 99%

“…Bradykinin, acting through its B 2 receptor, stimulates the release of nitric oxide, inflammatory cytokines, and tissue‐type plasminogen activator (t‐PA) 9 , 10 , 11 , 12 , 13 , 14 . Specifically, we have found that during CPB, bradykinin concentrations correlate inversely with mean arterial pressure (MAP) and directly with t‐PA 6 . Studies in animals suggest that bradykinin B 2 receptor antagonism inhibits reperfusion‐induced increases in vascular permeability and neutrophil recruitment 15 , 16 .…”

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confidence: 99%

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Contribution of Endogenous Bradykinin to Fibrinolysis, Inflammation, and Blood Product Transfusion Following Cardiac Surgery: A Randomized Clinical Trial

Balaguer

Byrne

et al. 2012

Clin Pharmacol Ther

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Bradykinin increases during cardiopulmonary bypass (CPB) and stimulates the release of nitric oxide, inflammatory cytokines, and tissue-type plasminogen activator (t-PA), acting through its B2 receptor. This study tested the hypothesis that endogenous bradykinin contributes to the fibrinolytic and inflammatory response to CPB and that bradykinin B2 receptor antagonism reduces fibrinolysis, inflammation, and subsequent transfusion requirements. Patients (N = 115) were prospectively randomized to placebo, ε-aminocaproic acid (EACA), or HOE 140, a bradykinin B2 receptor antagonist. Bradykinin B2 receptor antagonism decreased intraoperative fibrinolytic capacity as much as EACA, but only EACA decreased D-dimer formation and tended to decrease postoperative bleeding. Although EACA and HOE 140 decreased fibrinolysis and EACA attenuated blood loss, these treatments did not reduce the proportion of patients transfused. These data suggest that endogenous bradykinin contributes to t-PA generation in patients undergoing CPB, but that additional effects on plasmin generation contribute to decreased D-dimer concentrations during EACA treatment.

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Angiotensin-converting enzyme inhibition and smoking potentiate the kinin response to cardiopulmonary bypass

Abstract: Preoperative ACE inhibitors and smoking potentiate the kinin response to CPB and may contribute to the hemodynamic and fibrinolytic response observed during CPB.

Cited by 10 publications

References 25 publications

Postoperative acute kidney injury is associated with hemoglobinemia and an enhanced oxidative stress response

Postoperative acute kidney injury is associated with hemoglobinemia and an enhanced oxidative stress response

Bradykinin and Its Metabolite Bradykinin 1-5 Inhibit Thrombin-Induced Platelet Aggregation in Humans

Contribution of Endogenous Bradykinin to Fibrinolysis, Inflammation, and Blood Product Transfusion Following Cardiac Surgery: A Randomized Clinical Trial

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