Effects of Low-Dose Heparin Infusion on Arterial Endothelin-1 Release in Humans

Piatti, PierMarco; Monti, Lucilla D.; Valsecchi, G.; Conti, M.; Nasser, R.; Guazzini, Barbara; Fochesato, Elena; Phan, C. Van; Pontiroli, Antonio E.; Pozza, G.

doi:10.1161/01.cir.94.11.2703

Cited by 18 publications

(13 citation statements)

References 34 publications

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“…8,9,14,15,19 Morphometric analysis in this study does not demonstrate changes in arteriolar structure that provide a basis for the ameliorating effect of heparin treatment on coronary conductance. The magnitude of heparin effects on coronary conductance was moderate and anticipated associated changes in coronary lumen size exponentially smaller and within the SDs of the data.…”

Section: Discussioncontrasting

confidence: 58%

“…Abbreviations as in Figure 1. FGF and VEGF receptor binding, 11,12 upregulation of nitric oxide, 8,15 and interference with inhibition of angiogenesis. Heparin blocks inactivation of FGF-2, VEGF, and TGF-␤ 1 by ␣ 2 -macroglobulin, 9 interferes with endothelin and thrombospondin (which inhibit angiogenesis and promote vascular smooth muscle proliferation), 8,14,15 and strongly binds angiostatin and endostatin, powerful inhibitors of angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…8 In addition, heparin inhibits arterial thickening with hypertension 18 and injury through interactions with FGF-2 and TGF-␤ 1 . 8,9,19 Heparin lowers vascular resistance with hypertension 14,18 through interactions with several factors 14,15 that probably include FGF-2 and VEGF. 8,20 The purpose of this investigation was to determine whether heparin can modulate coronary angiogenesis and vascular responses with hypertension.…”

mentioning

confidence: 99%

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Effects of Chronic Heparin Administration on Coronary Vascular Adaptation to Hypertension and Ventricular Hypertrophy in Sheep

Flanagan

Aoyagi²,

Arnold³

et al. 1999

Circulation

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Section: Discussioncontrasting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of Chronic Heparin Administration on Coronary Vascular Adaptation to Hypertension and Ventricular Hypertrophy in Sheep

Flanagan

Aoyagi²,

Arnold³

et al. 1999

Circulation

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“…4,6,34 In the present study, we hypothesized that competitive binding of heparin to glycocalyx-associated proteins would affect the mechanotransduction of shear stress to the endothelium. We found that a clinically relevant dose of heparin (Ϸ50 U/kg of body weight) was associated with an increased clearance of large dextrans from the systemic circulation and a reduction in the duration of arteriolar vasodilation during reactive hyperemia in the mouse cremaster muscle.…”

Section: Discussionmentioning

confidence: 98%

Heparin Impairs Glycocalyx Barrier Properties and Attenuates Shear Dependent Vasodilation in Mice

et al. 2007

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Abstract-The endothelial glycocalyx is a hydrated mesh of polysaccharides and adsorbed plasma proteins that forms the true interface between the flowing blood and the endothelium. We hypothesized in the present study that competitive binding of heparin to glycocalyx-associated proteins would affect glycocalyx barrier properties and mechanotransduction of shear stress to the endothelium. In anesthetized mice, the clearance of 70-kDa dextrans from the circulation was increased (PϽ0.05 versus saline) 1 hour after heparin (1.25 U) and glycocalyx degradation with hyaluronidase (35 U; amount cleared in 30 minutes after saline: 11Ϯ5%; after heparin: 45Ϯ8%; after hyaluronidase: 30Ϯ3%). Clearance of 40-kDa dextrans increased (PϽ0.05 versus saline) to a lesser extent after both treatments (saline: 46Ϯ3%; heparin: 60Ϯ5%; hyaluronidase: 60Ϯ2%). The dilator response of second-order arterioles in cremaster muscle during reactive hyperemia was reduced for Յ90 minutes after heparin as reflected by a decrease (Pϭ0.008) in t 50 of diameter recovery, and this effect was associated with a diminished NO bioavailability. Infusion of hyaluronidase resulted in reductions (PϽ0.05) in baseline and peak reactive hyperemic diameter, whereas, despite an increase in wall shear rate at the beginning of reactive hyperemia, t 50 of diameter recovery was not affected. In conclusion, our data in mice show that a heparin challenge is associated with increased vascular leakage of dextrans and impaired arteriolar vasodilation during reactive hyperemia. Our data suggest that protein-heparan sulfate interactions are important for a functional glycocalyx.

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“…It is possible, however, that in diseased segments in which flow was measured, the vasodilator capacity of the resistance vessel is reduced because of the stenosis. We gave heparin to our patients before beginning coronary catheterization; this drug can interact with mediators of the vascular endothelium, ie, ET, and decreases plasma ET-1 levels, 30 possibly by a nitric oxide-mediated mechanism. 31 However, because of the experimental protocol, it was not possible to do the study without heparinization of the patients.…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic and Coronary Effects of the Endothelin Antagonist Bosentan in Patients With Coronary Artery Disease

et al. 1998

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Background-Endothelin is a potent endothelium-derived vasoconstrictor peptide with proliferative properties. Elevated levels of the peptide occur in coronary artery disease; however, its pathophysiological role as a regulator of coronary tone and structure is uncertain. Endothelin-receptor antagonists are specific tools to clarify this issue and might be useful in the treatment of coronary artery disease. Methods and Results-In a double-blind, placebo-controlled randomized study, we investigated the effects of the ET A /ET B endothelin-receptor antagonist bosentan or placebo on systemic and coronary hemodynamics in 28 patients with angiographically documented stable coronary artery disease by quantitative coronary angiography and an intracoronary Doppler guidewire. Bosentan 200 mg IV decreased systolic blood pressure (PϽ0.05), whereas heart rate increased slightly (PϽ0.05). Coronary diameter increased, particularly in vessels with no or mild angiographic changes (PϽ0.01). Glycerol trinitrate did not further dilate these segments, whereas coronary diameter increased significantly after nitrate in the placebo group. The increase in coronary diameter after bosentan correlated inversely with plasma LDL-cholesterol levels (PϽ0.01) in both stenotic and angiographically normal coronary segments. Coronary flow velocity did not change. Bosentan was well tolerated. Conclusions-Endogenous endothelin exerts a vasoconstrictor tone in epicardial coronary arteries of patients with coronary artery disease, as evidenced by the vasodilation exerted by the combined ET A /ET B endothelin-receptor antagonist bosentan under acute conditions. Bosentan can safely be given to these patients. Hence, further long-term studies are necessary to determine the therapeutic potential of endothelin-receptor antagonists in patients with coronary artery disease. (Circulation. 1998;98:2235-2240.)

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Effects of Low-Dose Heparin Infusion on Arterial Endothelin-1 Release in Humans

Abstract: The present study showed that it is possible to decrease ET-1 levels by use of low-dose heparin infusion in humans. This effect seems mediated by a simultaneous increase in nitric oxide levels and is completely reversed by a mild increase in insulin concentrations.

Cited by 18 publications

References 34 publications

Effects of Chronic Heparin Administration on Coronary Vascular Adaptation to Hypertension and Ventricular Hypertrophy in Sheep

Effects of Chronic Heparin Administration on Coronary Vascular Adaptation to Hypertension and Ventricular Hypertrophy in Sheep

Heparin Impairs Glycocalyx Barrier Properties and Attenuates Shear Dependent Vasodilation in Mice

Hemodynamic and Coronary Effects of the Endothelin Antagonist Bosentan in Patients With Coronary Artery Disease

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