Direct vasoconstriction and endothelium-dependent vasodilation. Mechanisms of acetylcholine effects on coronary flow and arterial diameter in patients with nonstenotic coronary arteries.

Hodgson, John Mc B.; Marshall, J. Jeffrey

doi:10.1161/01.cir.79.5.1043

Cited by 190 publications

(66 citation statements)

References 26 publications

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“…21 Hodgson, using methylene blue (an inhibitor of the action of EDRF) suggested that acetylcholine is capable of releasing EDRF in humans. 22 In clinical studies, intracoronary acetylcholine infusion constricts coronary arteries when there is angiographic evidence of atherosclerosis in the studied vessel.10-12 However, controversy exists regarding the response of "normal" coronary arteries.101113 Furchgott1 described the endothelium-dependent vasomotor response of arteries to acetylcholine in vitro throughout a specific dose range. Variation in dose and rate of acetylcholine infusion may account in part for the reported heterogenous response in patients.…”

Section: Diameter Responsesmentioning

confidence: 99%

Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease.

et al. 1990

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In animals, acetylcholine dilates normal arteries and produces vasoconstriction in the presence of hypercholesterolemia, hypertension, or atherosclerosis, reflecting endothelial cell dysfunc- (Circulation 1990;81:491-497) In animals, acetylcholine produces endotheliumdependent dilation of normal arteries and vasoconstriction in pathologic states such as hypersee p 697 cholesterolemia, hypertension, or atherosclerosis.1-9 Clinical studies have shown that intracoronary acetylcholine infusion constricts atherosclerotic coronary arteries.9-11 Smooth segments may also constrict in patients with coronary artery disease evident in

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Section: Diameter Responsesmentioning

confidence: 99%

Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease.

et al. 1990

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“…Infusion of acetylcholine (ACh) in vivo in the coronary circulation revealed that ACh has a dual action, causing vasodilatation at low and vasoconstriction at high doses in the baboon (Van Winkle & Feigl, 1989;Knight et al, 1991), cattle and man (Hodgson & Marshall, 1989;Knight et al, ' Author for correspondence. (Van Winkle & Feigl, 1989;Knight et al, 1991), and only vasoconstriction in the porcine coronary circulation (Kawamura et al, 1989;Cowan & McKenzie, 1990).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of muscarinic receptors in lamb isolated coronary resistance arteries

Simonsen

Prieto

Rivera

et al. 1993

British J Pharmacology

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1 In vitro experiments in a microvascular myograph were designed to characterize postjunctional muscarinic receptors producing contraction both in the presence and absence of the endothelium in coronary resistance arteries (normalized diameter of 150-450 jm), isolated from the left ventricle of hearts from 3-6 month old lambs. Preferential muscarinic receptor antagonists were used to determine the receptor subtype: pirenzepine (MI receptor), AFDX 116 (M2 receptor), 4-DAMP and pFHHSiD (M3 receptor). 2 The rank order of potency for muscarinic agonist-induced increases in tension in endothelium-intact preparations was oxotremorine-M = methacholine = acetylcholine (ACh) > carbachol. Removal of the endothelium increased the potency of ACh, but this procedure did not change either the sensitivity or maximal response to carbachol. 3 The contractile response to ACh was reproducible. Incubation with 3 x 10-7-3 x 10-6 M pirenzepine induced non-parallel rightward shifts and depressed the maximum of the concentration-response curve to ACh in endothelium-intact arteries. The slope by Schild analysis was 2.9 ± 0.8 (P <0.05, n = 7). Atropine, AFDX 116, 4-DAMP and pFHHSiD produced parallel rightward shifts of the curves to ACh and the slopes of the Schild plots were not significantly different from unity. The pKB values for the antagonists from plots constrained to unity in endothelium-intact segments were: atropine (9.4), 4-DAMP (9.0), pFHHSiD (7.9) and AFDX 116 (6.2). 4 In endothelium-denuded arteries, pirenzepine, AFDX 116 and pFHHSiD caused concentrationdependent, parallel rightward displacements of the concentration-response curves to ACh and the slopes of the Schild plots were not significantly different from unity. The plots constrained to a slope of unity gave the following pKB values: pFHHSiD (8.7), pirenzepine (7.5) and AFDX 116 (6.2). 5 In the presence of the endothelium, low concentrations of pirenzepine (10-9-1-' M) produced leftward shifts of the ACh concentration-response curves. This potentiating effect of pirenzepine was reversed by endothelial cell removal. In preparations precontracted with the thromboxane-mimetic, U46619, the putative MI-selective agonist, McN-A-343, induced a biphasic relaxation with log IC50 of 8.53 ± 0.14 and 5.02 ± 0.08 for the first and second phase of the relaxation, respectively, and maximal relaxations of 22.8 ± 4.3% and 41.1 ± 5.4% (n = 16). McN-A-343 relaxed the vessels in the presence of 10-' M pFHHSiD and 3 x 10-7 M AFDX 116, but not after incubation with 10-9 M pirenzepine.6 It is concluded from the pKB values for the antagonists used, that contraction induced by ACh in lamb coronary resistance arteries, in either the presence or the absence of the endothelium, is mediated via the M3 subtype of muscarinic receptors, while muscarinic receptors of another subtype at the endothelium seem to modulate the contractile response to ACh.

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“…However, the vascular response to ACh may not be caused solely by the release of endothelium-derived NO, but may also involve direct smooth muscle constriction; that is, the net effect of ACh on the human coronary vasculature is the result of a combination of both effects. 6 Therefore, as far as the 3 patients with HCM and coronary vasospasm are concerned, it is plausible that the AChinduced coronary vasocontractions were caused by the impaired release of endothelium-derived NO or enhanced direct smooth muscle constriction, or a combination.…”

Section: Coronary Vasomotor Responses To Achmentioning

confidence: 99%

“…4,5 However, ACh is not only an endothelium-dependent vasodilator, but can also serve as a potent vasoconstrictor in human coronary arteries. 6 The net vascular bed response to ACh depends on the interplay between both effects. Little information is currently available regarding coronary endothelial function in patients with HCM.…”

mentioning

confidence: 99%

Coronary Endothelium-Dependent and Independent Vasomotor Responses in Patients With Hypertrophic Cardiomyopathy

Yokohama

Matsumoto

Horie

et al. 2002

Circ J

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variety of mechanisms may contribute to the production of myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM) who have angiographically normal coronary arteries. Previous studies have reported that coronary vasospasm often occurs in these patients, 1-3 and endothelial dysfunction has been regarded as a key factor in the pathogenesis of coronary vasospasm in patients with coronary spastic angina because intracoronary injection of acetylcholine (ACh) induces coronary vasospasm. 4,5 However, ACh is not only an endothelium-dependent vasodilator, but can also serve as a potent vasoconstrictor in human coronary arteries. 6 The net vascular bed response to ACh depends on the interplay between both effects. Little information is currently available regarding coronary endothelial function in patients with HCM.On the other hand, there is a growing body of evidence that coronary flow reserve (CFR), estimated by various methods, is decreased in patients with HCM. [7][8][9][10][11][12] The question arises whether the endothelium-dependent vasomotor responses of coronary epicardial and resistance coronary arteries are impaired as a result of the dysfunction of coronary smooth muscle cells in patients with HCM. Bradykinin (BK) is an endothelium-dependent vasodilator and has no direct vasoconstricting effect in human coronary arteries. [13][14][15] and papaverine is an endothelium-independent vasodilator in human coronary arteries.The aim of this study was to elucidate the respective functions of coronary endothelial and smooth muscle cells in the coronary macro-and microcirculation in patients with HCM. Thus, we compared the vasomotor responses induced by the intracoronary infusion of ACh, BK and papaverine in both epicardial and resistance coronary arteries in HCM patients with those in control subjects. Methods Study PatientsThe study protocols were approved by the Ethical Committee on Human Research, and written informed consent was obtained from all participants. Fourteen patients with HCM and 11 control patients with atypical chest pain or myocardial ischemia on ECG were studied. The diagnosis of HCM was based on an echocardiography examination and microscopic findings of myocardial tissues 16 that were obtained from right ventricular endomyocardial biopsies. The echocardiographic findings in all of the HCM patients were asymmetrical hypertrophy of the septum, anterolateral free wall and apex (occasionally), without a left ventricular outflow tract pressure gradient on Doppler recordings. The criterion for the diagnosis of asymmetric septal hypertrophy was a septum ≥1.5 times the thickness of the posterior wall when measured in diastole just before atrial systole.None of the patients with HCM had significant organic stenosis angiographically. All of the control patients had atypical chest pain and angiographically normal coronary arteries. Patients with hypertension, hypercholesterolemia, diabetes mellitus, myocardial infarction, congestive heart Circ J 2002; 66: 30 -34 (Received June 21, 2001; revised ...

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Direct vasoconstriction and endothelium-dependent vasodilation. Mechanisms of acetylcholine effects on coronary flow and arterial diameter in patients with nonstenotic coronary arteries.

Cited by 190 publications

References 26 publications

Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease.

Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease.

Heterogeneity of muscarinic receptors in lamb isolated coronary resistance arteries

Coronary Endothelium-Dependent and Independent Vasomotor Responses in Patients With Hypertrophic Cardiomyopathy

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