Enhancement of Metabolic Coronary Dilatation by Aspirin-like Substances by Suppression of Prostaglandin Feedback Control?

Talesnik, J; Sunahara, F. A.

doi:10.1038/244351a0

Cited by 18 publications

(11 citation statements)

References 15 publications

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“…It can be seen that there was an initial brief period of diminished CF which was quickly overcome by a marked diminution in coronary resistance, giving rise to increased CF whose magnitude depended on the length and frequency of stimulation (Figures 4 and 5). The initial decrease of CF is not affected by the administration of a-adrenoceptor blocking agents (Talesnik & Sunahara, 1973).…”

Section: Resultsmentioning

confidence: 95%

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Coronary Reactions to Cardiac Hyperactivity and to Hypoxia in Isolated Perfused Heart of Rat

Sen

Sunahara

Talesnik

et al. 1977

British J Pharmacology

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I Continuous recording of cardiac force of contraction, heart rate and coronary flow from isolated perfused hearts of rats was used to study coronary reactions: (a) to cardiostimulation with noradrenaline, CaCl2, or electrically induced tachycardia; (b) to short duration stoppage of coronary inflow (hypoxia). 2 The heart rate was controlled by electrical pacing. Coronary vasodilatation resulted from cardiostimulation or hypoxia. This coronary response was greater at higher heart rates. 3 In parallel experiments administration of noradrenaline to hearts paced at different frequencies resulted in a rate-dependent elevation of adenosine-3',5'-cyclic monophosphate (cyclic AMP). 4 Duration of hypoxia leading to different degrees of reactive hyperaemia did not change the cardiac cyclic AMP levels. SCoronary vasodilatation due to increased cardiac metabolism produced by noradrenaline, Ca2+ or tachycardia was enhanced by the phosphodiesterase inhibitors diazoxide and papaverine while it was inhibited during the administration of prostaglandin E2. 6 Reactive hyperaemia was unaffected by diazoxide, papaverine or prostaglandin E2. 7 Catecholamine depletion by reserpine did not influence metabolic coronary dilatation nor the reactive hyperaemic responses. 8 We postulate that there are at least two types of coronary reactions: one in response to hypoxia, 'reactive hyperaemia', and another resulting from cardiac hyperactivity, 'metabolic coronary dilatation'. The latter, blocked by prostaglandin E2 and enhanced by diazoxide or papaverine, would be triggered by cyclic AMP while reactive hyperaemia would result from other mechanisms.

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Section: Resultsmentioning

confidence: 95%

“…We also investigated the possibility that the endogenously synthesized prostaglandin could be a modulator of the adenylate cyclase activation, thus explaining the augmented MCD responses obtained in isolated perfused hearts by giving aspirin-like substances (Talesnik & Sunahara, 1973).…”

Section: Introductionmentioning

confidence: 99%

Coronary Reactions to Cardiac Hyperactivity and to Hypoxia in Isolated Perfused Heart of Rat

Sen

Sunahara

Talesnik

et al. 1977

British J Pharmacology

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“…This slight diminution can be accounted for by the duration of the experiment. The unavoidable deterioration of the preparation, after 2 h of perfusion, has been shown to be a regular limitation of the Langen- dorff preparation (Aronson & Serlick, 1976 Influence of non-steroidal anti-inflammatory agents and arachidonic acid on coronary reactions to cardiostimulation or hypoxia Indomethacin (5 mg/l; 1.4 x 10-' M) or naproxen (25 mg/l; 1 x 10' M) were administered by slow infusion or at constant concentration in a series of experiments in which we tested the coronary reactions as previously described for indomethacin and aspirin (Talesnik & Sunahara, 1973). The immediate reaction of the coronaries was a transient but slight vasodilatation that subsided in about 5 to 10 min.…”

Section: Resultsmentioning

confidence: 99%

“…It must also be considered that exogenously administered AA may be metabolized to prostaglandins somewhat differently from endogenously released arachidonate although AA could easily be incorporated into the phospholipids of the intact heart (Isakson et al, 1977a). Thus, the explanation originally given by us for the enhancement (Talesnik & Sunahara, 1973) is incomplete in as much as inhibition of the prostaglandin-synthetase located in the myocardial cell is concerned.…”

Section: Effect Of Non-steroidal Anti-inflammatory Agents On the Reacmentioning

confidence: 99%

“…Since patients with 'normal' coronary arteries may show angina pectoris, with abnormal myocardial lactate metabolism, the diagnosis of 'small vessel disease' with changes in structure or dysfunction of structurally normal small arteries has been suggested (Schaper & Schaper, 1977); the lack of evidence nevertheless inclined other authors to revive the hypothesis of neurogenic vasospasm as a mechanism of coronary insufficiency (Yasue, Touyama, Shimamoto, Kato, Tanaka & Akiyama, 1974;Johnson & Detwiler, 1977;Hellstrom, 1977). We think that although metabolic factors in which prostaglandins may be involved, are often of great clinical significance in heart attacks (Marx, 1977), failure of the cor-onaries to adapt to increased 02 demands, should also be considered as a potential site for therapeutic tests (Talesnik & Sunahara, 1973). The modulation of the coronary responses by prostaglandins agrees with the concept of Silver & Smith (1975), in which prostaglandins are thought to act as intracellular messengers rather than local hormones or vasoactive substances acting on distant target cells.…”

Section: Effect Of Non-steroidal Anti-inflammatory Agents On the Reacmentioning

confidence: 99%

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Myocardial Synthesis of Prostaglandin‐like Substances and Coronary Reactions to Cardiostimulation and to Hypoxia

Sunahara

Talesnik

1979

British J Pharmacology

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1Continuous recording of cardiac contractions and coronary flow from isolated perfused hearts of rats permitted the study of coronary reactions to: (a) cardiostimulation induced by single doses or slow infusions of noradrenaline, CaCl2, glucagon or electrically induced tachycardia; (b) short interruptions of coronary inflow (hypoxia). 2 Except during tachycardia the heart rate was kept constant at 210 beats/min by electrical pacing. 3 Metabolic coronary vasodilatation (MCD) resulting from cardiac hyperactivity induced by noradrenaline, Ca2 +, tachycardia or glucagon was inhibited by administration of prostaglandin E2. Reactive hyperaemia response to hypoxia was unaffected by prostaglandin administration. 4 Inhibition of MCD could also be obtained by prolonged infusion with arachidonic acid (1.6 x 10'-M), presumably by its conversion into prostaglandin-like substance since arachidonic acid failed to block MCD in hearts from rats pretreated with non-steroidal anti-inflammatory drugs (indomethacin, naproxen, phenylbutazone). 5 Reactive hyperaemia was unaffected either by arachidonic acid or by blockade of the synthesis of prostaglandin-like substances by anti-inflammatory drugs. 6 Since prostaglandin synthetase inhibition does not prevent but may enhance MCD, we do not adtocate prostaglandin-like substances as agents directly responsible for the coronary vasodilatation that follows cardiac hyperactivity. 7 We postulate that cardiac overproduction of prostaglandins may lead to a failure in the adaptive coronary flow response to cardiac hyperactivity (coronary insufficiency?).

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Physiology and Pathophysiology of the Coronary Circulation and the Role of Nitroglycerin

Pitt¹

1975

Organic Nitrates

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Enhancement of Metabolic Coronary Dilatation by Aspirin-like Substances by Suppression of Prostaglandin Feedback Control?

Cited by 18 publications

References 15 publications

Coronary Reactions to Cardiac Hyperactivity and to Hypoxia in Isolated Perfused Heart of Rat

Coronary Reactions to Cardiac Hyperactivity and to Hypoxia in Isolated Perfused Heart of Rat

Myocardial Synthesis of Prostaglandin‐like Substances and Coronary Reactions to Cardiostimulation and to Hypoxia

Physiology and Pathophysiology of the Coronary Circulation and the Role of Nitroglycerin

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