Mechanisms of methacholine-induced coronary vasospasm in an experimental model of variant angina in the anesthetized rat

Vergona, Ronald; Herrott, Cynthia; Garippa, Ralph; Hirkaler, Gerard

doi:10.1016/0024-3205(84)90539-3

Cited by 4 publications

(5 citation statements)

References 10 publications

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“…In this model, clinically effective antianginal agents, such as calcium channel antagonists, nitrovasodilators [6,13] and nicorandil [14], prevented the ST-elevation, [12,15±19]. On the other hand, neither dipyridamole (vasodilator) nor propranolol (b-blocker) was effective in this model [12,13,16,20]. Interestingly, the ineffective- ness of these drugs in this model is consistent with their clinical directions for the treatment of vasospastic angina.…”

Section: Discussionsupporting

confidence: 63%

Effects of CP‐060S, a novel cardioprotective drug, in the methacholine‐induced ECG change model in rats

Fukazawa¹,

Adachi²,

Akima³

et al. 2001

Fundamemntal Clinical Pharma

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We compared the antianginal effect of CP-060S, a novel cardioprotective drug with Na+ and Ca2+ overload-preventing activity as well as Ca2+ channel antagonistic activity, with that of diltiazem, in an experimental model of vasospastic angina induced by methacholine in anaesthetized rats. Intra-aortic injection of methacholine at the coronary ostium provoked the ST-segment elevation of the electrocardiogram (ECG), indicating myocardial ischemia. CP-060S (3, 5 and 10 mg/kg, i.d.) significantly and dose-dependently suppressed the methacholine-induced ST-elevation, with the duration of action being at least 3 h at the highest dose. In addition, CP-060S at 3 mg/kg could inhibit the ST-elevation without producing significant changes in blood pressure, heart rate or rate-pressure product (RPP). In contrast, diltiazem (10 and 30 mg/kg, i.d.) significantly decreased the RPP, a significant suppression of the ST-elevation could only be achieved at the highest dose and its duration of action was about 2 h. Similar results were obtained with i.v. administration of the drugs, i.e. CP-060S given i.v. could inhibit the ST-elevation with less haemodynamic changes than diltiazem. In conclusion, CP-060S exerted a more potent and sustained protection against myocardial ischemia evoked by methacholine than diltiazem. The characteristics of the effects of CP-060S observed here suggest that this drug may be a desirable drug for the treatment of vasospastic angina.

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Section: Discussionsupporting

confidence: 63%

Effects of CP‐060S, a novel cardioprotective drug, in the methacholine‐induced ECG change model in rats

Fukazawa¹,

Adachi²,

Akima³

et al. 2001

Fundamemntal Clinical Pharma

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“…Angina refers to cardiac pain or discomfort triggered by strenuous activities. Several experimental angina models, such as vasopressin-, methacholine- and isoproterenol-induced angina models, have been used for studying angina [ 16 , 17 , 18 ]. Further, several indirect indicators such as ST-segment, blood pressure, and biochemical markers of myocardial injury are used to evaluate angina [ 29 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although several mechanisms, such as inflammation, apoptosis, microvascular dysfunction, and oxidative stress, are involved in I/R injury [ 15 ], the relationship of angina and I/R injury is still insufficiently understood. Even though vasopressin, methacholine, and isoproterenol, which evoke vasospasm, have been used as experimental animal models for angina [ 16 , 17 , 18 ], they have less translational potential.…”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species Cause Exercise-Induced Angina in a Myocardial Ischaemia-Reperfusion Injury Model

Wang

Kanda

Tsujino

et al. 2022

IJMS

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Percutaneous coronary intervention (PCI) effectively treats obstructive coronary artery syndrome. However, 30–40% patients continue to have angina after a successful PCI, thereby reducing patient satisfaction. The mechanisms underlying persistent angina after revascularisation therapy are still poorly understood; hence, the treatment or guideline for post-PCI angina remains unestablished. Thus, this study aimed to investigate the mechanisms underlying effort angina in animals following myocardial ischaemia-reperfusion (I/R) injury. Phosphorylated extracellular signal-regulated kinase (p-ERK), a marker for painful stimulation-induced neuronal activation, was used for the investigation. After a forced treadmill exercise (FTE), the number of p-ERK-expressing neurons increased in the superficial dorsal horn of the I/R model animals. Moreover, FTE evoked hydrogen peroxide (H2O2) production in the I/R-injured heart, inducing angina through TRPA1 activation on cardiac sensory fibres. Notably, the treatment of a TEMPOL, a reactive oxygen species scavenger, or TRPA1−/− mice successfully alleviated the FTE-induced p-ERK expression in the dorsal horn. The production of H2O2, a reactive oxygen species, through physical exercise contributes to angina development following I/R. Hence, our findings may be useful for understanding and treating angina following revascularisation therapy.

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“…Moreover, Vergona et al (1984) have cautioned against the use of methacholine-induced ischaemia for the screening of antianginal drugs as it may identify compounds with antimuscarinic activity (e.g. atropine).…”

Section: Discussionmentioning

confidence: 99%

“…The effect of Bay K 8644 on the ST segment amplitude was evident within 5-10 s after injection, (Vergona et al, 1984 5.0 tgkg-' (n = 12), 10.0 pgkg-' (n = 5). *P < 0.05, **P < 0.005.…”

Section: Introductionmentioning

confidence: 94%

Bay K 8644‐induced changes in the ECG pattern of the rat and their inhibition by antianginal drugs

Abraham

Amitai

et al. 1987

British J Pharmacology

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1 The effects of intracarotid administration of Bay K 8644 on the ECG pattern along with their reversal by antianginal drugs were investigated in anaesthetized rats. 2 Intracarotid injections of Bay K 8644(0.5-50.0 tgkg-') produced a dose-related transient increase in systemic blood pressure.3 The pressor response was accompanied by ST segment elevation (0.5-l0.0jgkg-'), ST segment depression concomitant with the occurrence of arrhythmias (20.0 figkg-'), or A-V block (50.0 ftgkg-').4 ST segment elevation reached its maximal value within 15 s and could be observed for 30-240 s. 5 The increase in blood pressure was immediate (within 5 s) and short lasting (30-120 s). After the initial increase it returned to control levels (0.5-20.0 gkg-') or dropped below (50.0ftgkg-').6 The ST segment elevation caused by 5.0 ggkg-' Bay K 8644 (submaximal dose) was blocked by antianginal drugs (e.g. nitroglycerin, nifedipine and diltiazem) and by the peripheral benzodiazepine receptor antagonist PK 11195. However, the pressor response was not blocked by any of the drugs used. 7 ST segment elevation (or depression) induced by intracarotid administration of Bay K 8644 provides a useful tool for the evaluation of potential antianginal drugs.

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Mechanisms of methacholine-induced coronary vasospasm in an experimental model of variant angina in the anesthetized rat

Cited by 4 publications

References 10 publications

Effects of CP‐060S, a novel cardioprotective drug, in the methacholine‐induced ECG change model in rats

Effects of CP‐060S, a novel cardioprotective drug, in the methacholine‐induced ECG change model in rats

Reactive Oxygen Species Cause Exercise-Induced Angina in a Myocardial Ischaemia-Reperfusion Injury Model

Bay K 8644‐induced changes in the ECG pattern of the rat and their inhibition by antianginal drugs

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