Inhibition of bradykinin‐induced vasodilation in human forearm vasculature by icatibant, a potent B2‐receptor antagonist.

Cockcroft, JR; Chowienczyk, Phil; Brett, SE; Bender, N.; Ritter, JM

doi:10.1111/j.1365-2125.1994.tb04360.x

Cited by 87 publications

(61 citation statements)

References 30 publications

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“…20 The present study extends these observations on the role of BK in vascular physiology. As reported previously in humans, 9 we observed that B 2 receptor antagonism specifically blocked BK-induced vasodilation; in addition, we observed that B 2 receptor antagonism blocked the effect of BK on tPA release from the forearm vascular endothelium.…”

Section: Discussionsupporting

confidence: 72%

“…We and others have shown that this dose inhibits the forearm vasodilator response to intra-arterial BK without affecting systemic blood pressure or HR. 9,10 Thirty minutes after completion of the HOE 140 infusion, intra-arterial infusions of SNP and BK were repeated. Pilot studies demonstrated that there was no tachyphylaxis to BK over this time interval.…”

Section: Protocol 1: Effect Of Bk Receptor Antagonismmentioning

confidence: 99%

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Bradykinin Stimulates Tissue Plasminogen Activator Release From Human Forearm Vasculature Through B ₂ Receptor–Dependent, NO Synthase–Independent, and Cyclooxygenase-Independent Pathway

et al. 2000

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Background-Bradykinin stimulates dose-dependent tissue plasminogen activator (tPA) release from human endothelium.Although bradykinin is known to cause vasodilation through B 2 receptor-dependent effects on NO, prostacyclin, and endothelium-derived hyperpolarizing factor production, the mechanism(s) underlying tPA release is unknown. Methods and Results-We measured the effects of intra-arterial bradykinin (100, 200, and 400 ng/min), acetylcholine (15, 30, and 60 g/min), and nitroprusside (0.8, 1.6, and 3.2 g/min) on forearm vasodilation and tPA release in healthy volunteers in the presence and absence of (1) the B 2 receptor antagonist HOE 140 (100 g/kg IV), (2) the NO synthase inhibitor L-N G -monomethyl-L-arginine (L-NMMA, 4 mol/min intra-arterially), and (3) the cyclooxygenase inhibitor indomethacin (50 mg PO TID). B 2 receptor antagonism attenuated vasodilator (Pϭ0.004) and tPA (Pϭ0.043) responses to bradykinin, without attenuating the vasodilator response to nitroprusside (Pϭ0.36). L-NMMA decreased basal forearm blood flow (from 2.35Ϯ0.31 to 1.73Ϯ0.22 mL/min per 100 mL, Pϭ0.01) and blunted the vasodilator response to acetylcholine (Pϭ0.013) and bradykinin (Pϭ0.07, Pϭ0.038 for forearm vascular resistance) but not that to nitroprusside (Pϭ0.47). However, there was no effect of L-NMMA on basal (Pϭ0.7) or bradykinin-stimulated tPA release (Pϭ0.45). Indomethacin decreased urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F 1␣ (Pϭ0.04). The vasodilator response to endothelium-dependent (Pϭ0.019 for bradykinin) and endotheliumindependent (Pϭ0.019) vasodilators was enhanced during indomethacin administration. In contrast, there was no effect of indomethacin alone (Pϭ0.99) or indomethacin plus L-NMMA (Pϭ0.36) on bradykinin-stimulated tPA release. Conclusions-These data indicate that bradykinin stimulates tPA release from human endothelium through a B 2 receptor-dependent, NO synthase-independent, and cyclooxygenase-independent pathway. Bradykinin-stimulated tPA release may represent a marker for the endothelial effects of endothelium-derived hyperpolarizing factor. (Circulation.

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Section: Discussionsupporting

confidence: 72%

Section: Protocol 1: Effect Of Bk Receptor Antagonismmentioning

confidence: 99%

Bradykinin Stimulates Tissue Plasminogen Activator Release From Human Forearm Vasculature Through B ₂ Receptor–Dependent, NO Synthase–Independent, and Cyclooxygenase-Independent Pathway

et al. 2000

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“…15 The study confirms prior studies with HOE 140 indicating that endogenous BK does not contribute to resting vascular tone. 12,19,21 However, this is the first study to demonstrate that ACE inhibition increases constitutive forearm endothelial t-PA release through an effect on endogenous BK.…”

Section: Discussionmentioning

confidence: 98%

“…This dose of HOE 140 has no effect on systemic blood pressure or heart rate, but blocks both the vasodilator and t-PA responses to infused BK for at least 3 hours. 11,19 FBF measurements and arterial and venous sampling were repeated after HOE 140. At this time, enalaprilat was infused in the brachial artery at a rate of 5 g/min.…”

Section: Experimental Protocolmentioning

confidence: 99%

Angiotensin-Converting Enzyme Inhibition Increases Human Vascular Tissue-Type Plasminogen Activator Release Through Endogenous Bradykinin

et al. 2003

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Background-Angiotensin-converting enzyme (ACE) inhibition potentiates the tissue-type plasminogen activator (t-PA) response to exogenous bradykinin. This study tested the hypothesis that ACE inhibition increases endothelial t-PA release through endogenous bradykinin. Methods and Results-We measured the effect of intra-arterial enalaprilat (5 g/min) on forearm blood flow (FBF) and net t-PA release before and during intra-arterial infusion of bradykinin (25 to 400 ng/min) and methacholine (3.2 to 12.8 g/min) in 24 smokers pretreated with bradykinin receptor antagonist HOE 140 (100 g/kg intravenously) or vehicle.There was no specific effect of HOE 140 on FBF or forearm vascular resistance (FVR, 29.9Ϯ3.6 versus 29.7Ϯ3.6 mm Hg · mL Ϫ1 · min Ϫ1 · 100 mL Ϫ1 after vehicle and HOE 140, respectively, Pϭ0.956 between groups). Resting FVR decreased during enalaprilat compared with vehicle or HOE 140, but not compared with baseline, and the effect was similar in the 2 groups (22.0Ϯ2.7 and 24.1Ϯ2.9 mm Hg · mL Ϫ1 · min Ϫ1 · 100 mL

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“…This dose has been shown to significantly blunt the vasodilatory response to intra-arterial bradykinin. 51 BP was determined using an automated oscillometric recording device every 5 min during the study (Dinamap, Critikon, Carlsbad, CA), using the average of three readings at each time point. Blood for biochemical analysis was collected 1 h before dialysis (T ϭ Ϫ60), at initiation of dialysis (T ϭ 0), 15 and 30 min after initiation of dialysis (T ϭ 15 and 30 min), at termination of dialysis (T ϭ 4 h), and 2 h after termination of dialysis (T ϭ 6 h).…”

Section: Study Protocolmentioning

confidence: 99%

Endogenous Bradykinin Contributes to Increased Plasminogen Activator Inhibitor 1 Antigen following Hemodialysis

Marney¹,

Ma²,

Luther

et al. 2009

Journal of the American Society of Nephrology

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Oxidative stress and inflammation predict cardiovascular events in chronic hemodialysis patients. Hemodialysis activates the kallikrein-kinin system, increasing bradykinin. Bradykinin promotes inflammation but also stimulates endothelial release of tissue-plasminogen activator and inhibits platelet aggregation. Understanding the detrimental and beneficial effects of endogenous bradykinin during hemodialysis has implications for the treatment of cardiovascular disease in the hemodialysis population. To test the hypothesis that bradykinin contributes to the inflammatory and fibrinolytic responses to dialysis, we conducted a double-blind, randomized, placebo-controlled crossover study comparing the effect of the bradykinin B 2 receptor blocker HOE-140 with vehicle on markers of oxidative stress, inflammation, fibrinolysis, and coagulation in nine hemodialysis patients without coronary artery disease. Bradykinin receptor antagonism did not affect the mean arterial pressure or heart rate response to dialysis. Monocyte chemoattractant protein 1 (MCP-1) peaked postdialysis; HOE-140 blunted the increase in MCP-1 (5.9 Ϯ 5.9 versus 25.6 Ϯ 20.1 pg/ml, P ϭ 0.01). HOE-140 also abolished the increase in plasminogen activator inhibitor 1 (PAI-1) antigen observed at the end of dialysis. In contrast, HOE-140 significantly accentuated the effect of dialysis on F 2 -isoprostanes and P-selectin. Taken together, these results suggest that endogenous bradykinin contributes to increases in MCP-1 and PAI-1 antigen after hemodialysis via its B 2 receptor. Factors that increase the production of bradykinin or decrease its degradation may enhance the inflammatory response to hemodialysis.

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Inhibition of bradykinin‐induced vasodilation in human forearm vasculature by icatibant, a potent B2‐receptor antagonist.

Abstract: 1 The effect of icatibant Thi5, Oic8]

Cited by 87 publications

References 30 publications

Bradykinin Stimulates Tissue Plasminogen Activator Release From Human Forearm Vasculature Through B ₂ Receptor–Dependent, NO Synthase–Independent, and Cyclooxygenase-Independent Pathway

Bradykinin Stimulates Tissue Plasminogen Activator Release From Human Forearm Vasculature Through B ₂ Receptor–Dependent, NO Synthase–Independent, and Cyclooxygenase-Independent Pathway

Angiotensin-Converting Enzyme Inhibition Increases Human Vascular Tissue-Type Plasminogen Activator Release Through Endogenous Bradykinin

Endogenous Bradykinin Contributes to Increased Plasminogen Activator Inhibitor 1 Antigen following Hemodialysis

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Inhibition of bradykinin‐induced vasodilation in human forearm vasculature by icatibant, a potent B2‐receptor antagonist.

Abstract: 1 The effect of icatibant Thi5, Oic8]

Cited by 87 publications

References 30 publications

Bradykinin Stimulates Tissue Plasminogen Activator Release From Human Forearm Vasculature Through B 2 Receptor–Dependent, NO Synthase–Independent, and Cyclooxygenase-Independent Pathway

Bradykinin Stimulates Tissue Plasminogen Activator Release From Human Forearm Vasculature Through B 2 Receptor–Dependent, NO Synthase–Independent, and Cyclooxygenase-Independent Pathway

Angiotensin-Converting Enzyme Inhibition Increases Human Vascular Tissue-Type Plasminogen Activator Release Through Endogenous Bradykinin

Endogenous Bradykinin Contributes to Increased Plasminogen Activator Inhibitor 1 Antigen following Hemodialysis

Contact Info

Product

Resources

About

Bradykinin Stimulates Tissue Plasminogen Activator Release From Human Forearm Vasculature Through B ₂ Receptor–Dependent, NO Synthase–Independent, and Cyclooxygenase-Independent Pathway

Bradykinin Stimulates Tissue Plasminogen Activator Release From Human Forearm Vasculature Through B ₂ Receptor–Dependent, NO Synthase–Independent, and Cyclooxygenase-Independent Pathway