The Release of a Coronary Vasodilator Metabolite From the Guinea‐pig Isolated Perfused Heart Stimulated by Catecholamines, Histamine and Electrical Pacing and by Exposure to Anoxia

1The effects of histamine have been studied on human isolated coronary artery preparations taken from hearts ranging in age from 9 to 73 years. 2 Histamine in large concentrations (100 jiM) contracted arteries which were without tone or spontaneous activity and sometimes induced rhythmic contractile activity. If spontaneous rhythmic activity was present it was enhanced by histamine. The contractile effects of histamine were inhibited by mepyramine but not by cimetidine. 3 Arteries which were contracted by depolarization responded with relaxation to histamine concentrations lower than those required to evoke a contraction; arteries from younger hearts were more sensitive than those from older hearts. 4 Mepyramine potentiated the maximal relaxant effect of histamine in arteries from hearts of all ages but cimetidine had very little effect. 5 In the presence of mepyramine, cimetidine antagonized the relaxant effect of histamine, shifting the concentration-effect curve to the right. 6 It is concluded that human coronary arteries contain both H1-and H2-type receptors, the HI-receptors mediating contraction. The relaxant effects of histamine can only be inhibited by a combination of both H1-and H2-receptor antagonists.

Section: Discussionmentioning

confidence: 72%

Effects of histamine and the histamine antagonists mepyramine and cimetidine on human coronary arteries in vitro

Godfraind

Miller

1983

“…The RH produced at 10 and 20 s is shown in Figure 7; . The concept of 'metabolic coronary dilatation' (MCD) is well recognized and included in many updated discussions on cardiovascular control (Vatner & Braunwald, 1975) but the question as to the mechanisms involved in this process is still open (Broadley, 1976). According to the adenosine hypothesis (Rubio & Berne, 1969;Rubio, Wiedmeier & Berne, 1974) the reduction in myocardial 02 tension, or increased cardiac metabolic activity, would lead to breakdown of adenine nucleotides to adenosine or to its synthesis in the extramyocardial cell space (Nakatsu & Drummond, 1972).…”

Section: Resultsmentioning

confidence: 99%

“…The latter results from a prolonged vasodilatation due to the action on the vasculature of certain metabolite(s) produced during the cardiac hyperactivity (Gregg & Fisher, 1963;Broadley, 1976). The intracardiac metabolic processes relating the cardiac hyperactivity to the enhancement of CF have been attributed to the increased level of cardiac adenosine-3',5'-cyclic monophosphate (cyclic AMP) (Sen, Sunahara & Talesnik, 1976).…”

Section: Introductionmentioning

confidence: 99%

“…In the present paper, we tested this hypothesis further by examining the influence of different initial left ventricle distentions and of heart rate on the MCD response, as well as the level of cyclic AMP produced by cardiostimulation at different heart rates. It has been shown that the increase in heart rate results in an augmentation of CF (Pitt & Gregg, 1968;Cobb, Bache, Curry, Ebert, McHale & Greenfield, 1973;Broadley, 1976), but that changes in heart rate have relatively little influence on coronary extravascular support (Raft, Kosche & Lochner, 1972). A distinction is also made between MCD (as a response to increase in cardiac metabolism) and 'reactive hyperaemia (RIH) that results from myocardial hypoxia.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Sen

Sunahara

Talesnik

et al. 1977

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.

“…The mechanism responsible for the diminution in coronary resistance in response to increased cardiac metabolism remains unknown. Although the adenosine hypothesis of Berne (1975) is continuously under critical evaluation (Moir & Downs, 1972) the consensus is that the coronary vasodilatation could be due to the action on the vasculature of certain unidentified metabolite(s) produced during the cardiac hyperactivity (Broadley, 1976).…”

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

confidence: 99%

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

Sunahara

Talesnik

1979

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?).