MYOCARDIAL SYNTHESIS OF PROSTAGLANDIN-LIKE SUBSTANCES AND CORONARY REACTIONS TO CARDIOSTIMULATION AND TO HYPOXIA

Continuous 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). Except during tachycardia the heart rate was kept constant at 210 beats/min by electrical pacing. 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. Inhibition of MCD could also be obtained by prolonged infusion with arachidonic acid (1.6 × 10−7m), 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). Reactive hyperaemia was unaffected either by arachidonic acid or by blockade of the synthesis of prostaglandin‐like substances by anti‐inflammatory drugs. Since prostaglandin synthetase inhibition does not prevent but may enhance MCD, we do not advocate prostaglandin‐like substances as agents directly responsible for the coronary vasodilatation that follows cardiac hyperactivity. We postulate that cardiac overproduction of prostaglandins may lead to a failure in the adaptive coronary flow response to cardiac hyperactivity (coronary insufficiency?). 1979 British Pharmacological Society