Absence of role of endothelium in the response of isolated porcine coronary arteries to acetylcholine

Gräser, T; Leisner, H; Tiedt, N

doi:10.1093/cvr/20.4.299

Cited by 38 publications

(20 citation statements)

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“…29 In contrast, the effect of acetylcholine on porcine vessels is at least partially endothelium independent. 30 In our experiments, acetylcholine induced vasoconstriction both in control vessels and in atherosclerotic vessels. This could either indicate endothelial dysfunction of the control vessels or indicate that acetylcholine is a vasoconstrictor of human arterioles with a diameter Ͻ100 m. Interestingly, histamine caused maximal vasodilatation in control vessels.…”

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confidence: 53%

Endothelial Dysfunction of Coronary Resistance Arteries Is Improved by Tetrahydrobiopterin in Atherosclerosis

et al. 2000

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Background-Tetrahydrobiopterin (BH4), an essential cofactor for the synthesis of NO, improves endothelial dysfunction after ischemia/reperfusion. Therefore, we hypothesized that reduction of BH4 is involved in the attenuation of endothelium-dependent vasodilation in atherosclerosis, and we investigated the effect of alterations of the BH4 level on the vasodilatory potential of coronary resistance vessels from humans and pigs with atherosclerosis. Methods and Results-Coronary arterioles were obtained from patients undergoing CABG (atherosclerosis group) or valve replacement (control group) and from pigs fed either a standard diet (control group) or atherogenic diet (atherosclerosis group). After isolation, vessels were cannulated, pressurized, and placed on the stage of an inverted microscope. Dose-response curves were investigated in response to the endothelium-dependent agonists histamine, serotonin, and acetylcholine (for pigs, substance P) and to the endothelium-independent agonist sodium nitroprusside (SNP) under control conditions and before and after incubation of the vessels with sepiapterin (substrate for BH4 synthesis). In vessels from patients and from animals with atherosclerosis, compared with vessels from the control groups, there was a significant (PϽ0.05) reduction of vasodilation to all tested endothelium-dependent agonists but not to SNP. After application of sepiapterin, the responses to the endothelium-dependent agonists but not to SNP were significantly improved in vessels from the atherosclerosis groups. Sepiapterin did not influence vascular reactivity in the control groups. Conclusions-Atherosclerosis severely compromises endothelial function of coronary resistance arteries. Administration of sepiapterin leads to a significant improvement of endothelium-dependent vasodilatation to different agonists in vessels from humans and pigs with atherosclerosis. Therefore, we conclude that a reduced availability of BH4 is involved in the development of endothelial dysfunction in atherosclerosis.

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confidence: 53%

Endothelial Dysfunction of Coronary Resistance Arteries Is Improved by Tetrahydrobiopterin in Atherosclerosis

et al. 2000

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“…13- 16 It is known that in porcine coronary arteries, acetylcholine does not cause endothelium-dependent relaxations due to the lack of cholinergic receptors on the endothelium. 36 Fifth, because it was difficult to perform immunostainings…”

Section: Study Limitationsmentioning

confidence: 99%

Association of Adventitial Vasa Vasorum and Inflammation With Coronary Hyperconstriction After Drug-Eluting Stent Implantation in Pigs In Vivo

Nishimiya

Matsumoto

Shindo

et al. 2015

Circ J

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Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jpIn order to reduce the adverse effects of the first-generation DES, many efforts have been made, including the development of a newer biocompatible DES. 9 Biolimus-A9 eluting stent (BES) is one of the new-generation DES with unique characteristics, such as biodegradable polymers that are absorbed into the arterial wall approximately 6 months after stent implantation. 9-11 Although BES has recently been shown to preserve ex-vivo coronary vasomotion as compared with SES in the short-term observations in pigs 12 and humans, 7 its mechanism remains largely unknown.We have previously demonstrated that Rho-kinase activation is a central molecular mechanism of coronary spasm in he widespread utilization of drug-eluting stents (DES) has remarkably reduced the risk of re-stenosis and of repeated revascularization. 1 However, the first-generation DES with durable polymers, such as sirolimus-eluting stents (SES), have no beneficial prognostic effects as compared with bare metal stents 2 or even cause unfavorable effects, such as stent thrombosis 3,4 and coronary hyperconstricting responses, 5-8 not only to acetylcholine, 5 but also to exercise 6 and atrial pacing. Background: The importance of adventitial inflammation has been implicated for the pathogenesis of coronary artery disease. However, the roles of adventitial changes in drug-eluting stent (DES)-induced coronary hyperconstriction remain largely unknown. In the present study, this issue in pigs in vivo with a special reference to adventitial vasa vasorum (VV) formation and Rho-kinase activation, a central mechanism of coronary vasospasm, was examined.

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“…The control group (32±+6 kg, n=13) was fed a regular chow, and the atherosclerotic group (40+-7 kg, n=13) was fed the regular chow supplemented with fat and cholesterol (sodium cholate, 1.5%; cholesterol, 3%; corn oil, 5.5%; grain, 18%; dried milk, 20%; lard, 24%; and sugar, 28%) for [16][17][18][19][20] weeks. The high lipid portion constituted -30-50% of the total diet.…”

Section: General Preparationmentioning

confidence: 99%

Pathophysiological consequences of atherosclerosis extend into the coronary microcirculation. Restoration of endothelium-dependent responses by L-arginine.

Davis

Cannon

et al. 1992

Circulation Research

205

108

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The goals of this study were 1) to quantitate the effects of atherosclerosis on physiological and pharmacological endothelium-dependent vasoactive responses in coronary arterioles downstream from arterial lesions and 2) to determine if administration of L-arginine, the precursor for endothelium-derived relaxing factor, would restore normal endothelium-dependent function. Dietary-induced atherosclerosis was induced in pigs, and vasomotor responses of isolated, cannulated coronary arterioles (30-70 ,um in diameter) were assessed by measuring diameter changes in vitro. To assess pharmacological alterations of endothelium-dependent responses, dose-response curves were constructed to ADP, serotonin, and histamine. To assess physiological alterations in endothelial function, different flow rates were established across the vessel. Arteriolar diameters were measured in vessels from normal and atherosclerotic pigs under control conditions, after administration of L-arginine, and after endothelial denudation. In arterioles from normal pigs, administration of serotonin, histamine, or ADP produced dose-dependent vasodilation, which was abolished by endothelial denudation. In arterioles from atherosclerotic pigs, administration of histamine, serotonin, and ADP produced dilation at only the highest doses (10-6_10-7 M), and the extent of dilation was only 20-30%Yo of that observed in arterioles from normal pigs. Initiation of flow also produced vasodilation in arterioles from normal pigs that was completely abolished after endothelial denudation. In arterioles from atherosclerotic pigs, flow-induced responses were absent. These abnormal physiological and pharmacological responses (i.e., blunted vasodilation to pharmacological stimulation and to flow) were restored after administration of L-arginine for 40 minutes. The vascular responses after administration of L-arginine were not different from those observed under control conditions in arterioles from normal pigs. In addition, L-arginine did not restore vasodilation to the endothelium-dependent agonists in denuded segments. From these data in arterioles downstream from atherosclerotic lesions, we conclude that 1) the ED50 and maximal responses of endothelium-dependent vasodilation to ADP, histamine, and serotonin are attenuated; 2) the physiological response to flow, that is, flow-mediated endothelium-dependent vasodilation, is absent; and 3) the abnormality in arteriolar responsiveness during large vessel disease involves an impairment of the synthesis and/or release of endothelium-derived relaxing factor. (Circulation Research 1992;70:465-476) KEY WoRDs * coronary circulation * coronary microcirculation * endothelium-dependent responses * atherosclerosis * vasodilation, flow-induced * arteriole * endothelium-derived relaxing factor A therosclerosis is known to potentiate the vasoconstrictor responses of arteries to several ago-

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Absence of role of endothelium in the response of isolated porcine coronary arteries to acetylcholine

Cited by 38 publications

References 0 publications

Endothelial Dysfunction of Coronary Resistance Arteries Is Improved by Tetrahydrobiopterin in Atherosclerosis

Endothelial Dysfunction of Coronary Resistance Arteries Is Improved by Tetrahydrobiopterin in Atherosclerosis

Association of Adventitial Vasa Vasorum and Inflammation With Coronary Hyperconstriction After Drug-Eluting Stent Implantation in Pigs In Vivo

Pathophysiological consequences of atherosclerosis extend into the coronary microcirculation. Restoration of endothelium-dependent responses by L-arginine.

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