Human Coronary Arteriolar Dilation to Bradykinin Depends on Membrane Hyperpolarization

Miura, Hiroto; Liu, Yanping; Gutterman, David D.

doi:10.1161/01.cir.99.24.3132

Cited by 179 publications

(178 citation statements)

References 55 publications

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“…Although BK and MCh act through unique receptors (B 2 and M 3 , respectively), both agonists act through G␣ q to activate phospholipase C and stimulate the production of inositol triphosphate. 22 Both BK 23 and MCh 17 stimulate the release of endothelium-derived hyperpolarizing factor. As reported previously, 18 MCh significantly increased t-PA release, as well as FBF.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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“…Bradykinin has already been reported to hyperpolarize smooth muscle cells in human coronary arteries, 11 and this hyperpolarization could not be attributed to NO. 12,13 …”

mentioning

confidence: 99%

Mediators of Bradykinin-Induced Vasorelaxation in Human Coronary Microarteries

Batenburg¹,

Garrelds²,

Kats³

et al. 2004

Hypertension

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Abstract-To investigate the mediators of bradykinin-induced vasorelaxation in human coronary microarteries (HCMAs), HCMAs (diameter Ϸ300 m) obtained from 42 heart valve donors (20 men and 22 women; age range, 3 to 65 years; mean age, 46 years) were mounted in Mulvany myographs. In the presence of the cyclooxygenase inhibitor indomethacin, bradykinin relaxed preconstricted HCMAs in a concentration-dependent manner. N G -nitro-L-arginine methyl ester and ODQ (inhibitors of nitric oxide [NO] synthase and guanylyl cyclase, respectively) and the NO scavenger hydroxocobalamin, either alone or in combination, shifted the bradykinin concentration-response curve to the right. Removal of H 2 O 2 (with catalase), inhibition of cytochrome P450 epoxygenase (with sulfaphenazole or clotrimazole) or gap junctions (with 18␣-glycyrrhetinic acid or carbenoxolone), and blockade of large-(BK Ca ) and small-(SK Ca ) conductance Ca 2ϩ -dependent K ϩ channels (with iberiotoxin and apamin), either alone or in addition to hydroxocobalamin, did not affect bradykinin. In contrast, complete blockade of bradykinin-induced relaxation was obtained when we combined the nonselective BK Ca and intermediate-conductance (IK Ca ) Ca 2ϩ -dependent K ϩ channel blocker charybdotoxin and apamin with hydroxocobalamin. Charybdotoxin plus apamin alone were without effect. Inhibition of inwardly rectifying K ϩ channels (K IR ) and Na ϩ /K ϩ -ATPase (with BaCl 2 and ouabain, respectively) shifted the bradykinin concentration-response curve 10-fold to the right but did not exert an additional effect in the presence of hydroxocobalamin. In conclusion, bradykinin-induced relaxation in HCMAs depends on (1) the activation of guanylyl cyclase, K IR , and Na ϩ /K ϩ -ATPase by NO and (2) IK Ca and SK Ca channels. The latter are activated by a factor other than NO. This factor is not a cytochrome P450 epoxygenase product or H 2 O 2 , nor does it depend on gap junctions or BK Ca channels. Key Words: bradykinin Ⅲ arteries Ⅲ endothelium-derived factors Ⅲ nitric oxide E ndothelium-dependent relaxation induced by bradykinin cannot fully be attributed to the release of nitric oxide (NO). In resistance-size vessels, a large proportion of endothelium-derived relaxation involves the release of endothelium-derived hyperpolarizing factors (EDHFs). 1 Putative EDHF candidates are prostacyclin, S-nitrosothiols, K ϩ , cytochrome P450 products of arachidonic acid (epoxyeicosatrienoic acids [EETs]), and H 2 O 2 , 2-8 and EDHF-dependent responses have been reported to involve large-, intermediate-, and/or small-conductance Ca 2ϩ -activated K ϩ channels (BK Ca , IK Ca , and SK Ca, respectively), inwardly rectifying K ϩ (K IR ) channels, Na ϩ /K ϩ -ATPase, and gap junctions. 4,5,8 -10 Busse et al 9 recently summarized all currently available data on EDHF and proposed that EDHF-mediated relaxation (ie, relaxation observed in the absence of NO) depends on the activation of endothelial IK Ca and SK Ca channels. 4 Such activation results in the release of K ϩ into the myoendothelial spac...

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“…1,4,6,7 Briefly, isolated microvessels (50 to 200 m in diameter) were transferred to a 20-mL organ chamber containing Krebs solution of the following composition (in mM/L): NaCl 118, KCl 4.7, CaCl 2 2.5, KH 2 PO 4 1.2, MgSO 4 1.2, NaHCO 3 20, Na 2 EDTA 0.026, and glucose 11, pH 7.4. Each end of the arteriole was secured to a separate glass micropipette (25-to 50-m internal diameter) filled with Krebs buffer 8 and transferred to the stage of an inverted microscope (CK2; Olympus) coupled to a charge-coupled device camera (WV-BL200, Panasonic) and video micrometer (VIA-100K; Boeckeler Instruments, Inc).…”

Section: Videomicroscopymentioning

confidence: 99%

“…1,4,6,7 Approximately 2 mL of warmed air was infused through the vessel over a 2-minute period. This was immediately followed by warmed physiological saline solution to fill the vessel and remove all air bubbles.…”

Section: Endothelial Denudation Morphological Assessment and Stimulmentioning

confidence: 99%

Novel Mechanism of Vasodilation in Inflammatory Bowel Disease

Hatoum

Gauthier

Binion

et al. 2005

ATVB

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Objective-Endothelium-dependent dilation to acetylcholine (Ach) is reduced in mucosal arterioles from patients with inflammatory bowel disease (IBD). The contributions of both nitric oxide (NO) and endothelial-derived hyperpolarizing factor (EDHF) are decreased. We hypothesized that the remaining dilation results from products of cyclooxygenase. Methods and Results-High-performance liquid chromatography (HPLC) was used to isolate eicosanoid vasodilator products and videomicroscopy was used to examine vasomotor responses in human mucosal arterioles from subjects with or without IBD undergoing bowel resection surgeries. In subjects without IBD, Ach constricted (Ϫ52%Ϯ10%) arterioles devoid of endothelium. Indomethacin (INDO) (cyclooxygenase inhibitor) had no effect. In contrast, Ach dose-dependently dilated both intact and endothelial denuded arterioles from patients with IBD. The dilation was converted to constriction by INDO (Ϫ54%Ϯ9%; PϽ0.05 versus non-IBD) or by BWA868C (PGD 2 receptor antagonist). Only in arterioles from subjects with IBD did Ach produce an arachidonic acid metabolite that comigrated on HPLC with PG D 2 (PGD 2 ). Exogenous PGD 2 dilated (maxϭ66%Ϯ4%) IBD arterioles. Conclusion-In arterioles from IBD patients, Ach-mediated dilation shifts from endothelial production of NO and EDHF to nonendothelial generation of a PG, likely PGD 2 . This is a novel dilator mechanism arising from nonendothelial vascular tissue that compensates for loss of endothelium-dependent dilation. PGD 2 appears to be important in regulating mucosal blood flow in patients with IBD, implicating potentially detrimental effects from nonsteroidal antiinflammatory drugs. Key Words: cyclooxygenase Ⅲ inflammatory bowel disease Ⅲ microcirculation Ⅲ prostaglandin Ⅲ vasodilation E ndothelium-dependent vasorelaxation plays a critical role in regulating tissue perfusion. 1 Impaired vasorelaxation is a key feature of microvascular dysfunction that contributes to the pathophysiology of diabetes mellitus, hyperlipidemia, and atherosclerosis. 2,3 A new association of microvascular dysfunction with clinical inflammatory bowel disease (IBD) (Crohn disease, ulcerative colitis) has been made. 4 IBD is characterized by refractory, poorly healing mucosal ulcerations, and impaired endothelium-mediated vasorelaxation. 4,5 Using in vitro dimension measurements of cannulated 50 to 200 m arterioles, we have demonstrated that normal intestinal microvessels dilate in response to the classic endothelium-dependent agonist, acetylcholine (Ach). 4 After inhibiting nitric oxide (NO) synthase, cyclooxygenase (COX), and hyperpolarization mechanisms, or after endothelial denudation, constriction was observed. Microvessels isolated from chronically inflamed IBD tissue demonstrated loss of NO-mediated and hyperpolarization-mediated vasodilation in response to Ach. However, in contrast to vessels from subjects without IBD or from uninvolved segments of bowel from patients with IBD, arterioles from active IBD segments had attenuated dilation to Ach that was independ...

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Human Coronary Arteriolar Dilation to Bradykinin Depends on Membrane Hyperpolarization

Cited by 179 publications

References 55 publications

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

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

Mediators of Bradykinin-Induced Vasorelaxation in Human Coronary Microarteries

Novel Mechanism of Vasodilation in Inflammatory Bowel Disease

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