The effect of metabolic inhibitors on the response of the perfused rat heart to epinephrine

Horn, Richard; Aronson, Carl E.; Hess, Marilyn E.; Haugaard, Niels

doi:10.1016/0006-2952(67)90008-1

Cited by 16 publications

(10 citation statements)

References 5 publications

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“…The spontaneous relaxation has a high energy of activation, similar to that found for the spontaneous relaxation of the potassium contracture in frog skeletal muscle (Caputo, 1972) but less than that found for the same phenomenon in frog heart or for the binding of calcium by isolated sarcoplasmic reticulum (Chapman, 1973b;Inesi & Watanabe, 1967). The idea of non-homogeneity in the relaxing system has been advanced for skeletal muscle (Winegrad, 1970;Caputo, 1972), while in heart muscle this proposal is made often in an attempt to involve the mitochondria in the relaxation system (Chance, 1965;Horn, Aronson, Hess & Haugaard, 1967;Horn, Levin & Haugaard, 1968). More recently the need for a functional division of the sarcoplasmic reticulum in heart muscle has been voiced (Chapman & Miller, 1971;Tritthart, Kaufmann, Volkmer, Bayer & Krause, 1973).…”

Section: Discussionmentioning

confidence: 88%

The time‐dependent and dose‐dependent effects of caffeine on the contraction of the ferret heart

Chapman¹,

Léoty²

1976

The Journal of Physiology

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SUMMARY1. Trabeculae isolated from ferret heart and from other mammalian hearts have been mounted in a way that enables the tension generated to be measured while the composition of the bathing fluid is rapidly altered.2. Application of caffeine to these trabeculae initiates a rapid transient contracture and depresses the strength of regularly evoked heart beats.3. The strength of the contractures, the rate of tension development and the rate of spontaneous relaxation are all increased by raising the concentration of the applied caffeine.4. The strength of the caffeine contracture is relatively unaffected by changes in the bathing Na+, K+ or Ca2+ concentrations, but is reduced by exposure to the free-base form of local anaesthetics.5. Lowering of the temperature has complex effects on the amplitude of the caffeine contracture due to the differing temperature sensitivities of the contraction and spontaneous relaxation.6. Following a caffeine contracture, a period of perfusion by caffeinefree solution is required before a full-sized contracture can be evoked by the re-application of caffeine. This re-priming of the caffeine contracture has a sigmoidal time course that can be fitted by a two compartment model. The rate constants of the filling of each of the compartments can be obtained analytically, and are found to be increased by raising the extracellular calcium concentration, [Ca]o, by stimulating the preparation or by raising the temperature. Reducing the [Na]o or raising the [K]0 has little effect on these processes.7. The presence of traces of caffeine in the perfusing fluid between the conditioning and test challenges with the caffeine contracture solution reduces the extent of the re-priming without much affecting its rate.

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Section: Discussionmentioning

confidence: 88%

The time‐dependent and dose‐dependent effects of caffeine on the contraction of the ferret heart

Chapman¹,

Léoty²

1976

The Journal of Physiology

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“…Actions of noradrenaline on the contractile strength seemed to be additive to the actions of a rise in [Ca++] (Horn, Aronson, Hess & Haugaard, 1967). It has also been shown that mechanical responses of isolated rat ventricles to adrenaline is markedly reduced by metabolic inhibitors such as fluorodinitrobenzene, an inhibitor of ATP and creatine phosphotransferase (Infante & Davies, 1965), and sodium fluoride, a well known inhibitor of the Embden-Meyerhof pathway (Dhalla & Braxton, 1968).…”

Section: Discussionmentioning

confidence: 99%

Effects of calcium, sodium and potassium ions on contractility of isolated atria and their responses to noradrenaline

Toda

1969

British J Pharmacology

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1. Rabbit left atrial preparations driven electrically at different rates were used for studies on inotropic effects of cations, drugs and coupled pacing. Sino-atrial node-atrial preparations were used for investigating the chronotropic effect of noradrenaline. 2. The contractile tension-driving rate relationship was moved upwards by an elevation of [Ca++]o, coupled pacing and noradrenaline. In preparations exposed to Na+-poor and K+.free solutions the contractile strength alt low driving rates (6 to 30 c/min) was markedly enhanced, but at high rates (120 to 240 c/min) it was not influenced. The contractile strength was reduced at low [Ca++]

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“…We have previously reported the levels of glycolytic intermediates, adenine nucleotides and creatine phosphate as well as effluent lactate in hearts perfused with either iodoacetate or fluoroacetate (Horn et al 1967). Surprisingly, in the absence of adrenaline iodoacetate did not reduce the production of lactate from endogenous glycogen in spite of a clear inhibition of GAPDH.…”

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confidence: 83%

“…

During studies performed in Haugaards laboratory (Horn et al 1967(Horn et al , 1969 on the effect of catecholamines upon the perfused rat heart the unexpected observation was made that a number of metabolic inhibitors increased the reactivity of the phosphorylase system to adrenaline. In the presence of iodoacetate, fluoroacetate, rotenone and oligomycin the effect of adrenaline on the conversion of phosphorylase b to a was greater than that seen in control hearts.

…”

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confidence: 96%

Metabolic Regulation of the Response of the Glycogen Phosphorylase System to Hormones in Rat Heart and Diaphragm

Horn

Høstmark

1974

Acta Endocrinologica

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During studies performed in Haugaards laboratory (Horn et al. 1967(Horn et al. , 1969 on the effect of catecholamines upon the perfused rat heart the unexpected observation was made that a number of metabolic inhibitors increased the reactivity of the phosphorylase system to adrenaline. In the presence of iodoacetate, fluoroacetate, rotenone and oligomycin the effect of adrenaline on the conversion of phosphorylase b to a was greater than that seen in control hearts. \l=O/\ye (1967) has reported that anoxia has a similar effect upon the prefused rat heart. One question that these observations raised was that of receptor specificity: was this effect of metabolic inhibition limited to modification of the effects of catecholamines? We have therefore exposed perfused hearts to low doses of glucagon and have observed that the same sort of effects can be seen following stimulation of the isolated perfused heart with this polypeptide hormone (Table 1). In the presence of 1 mM iodoacetate, glucagon increased phosphorylase a levels by more than 3 times that seen in the absence of the inhibitor. Our working hypothesis has been that the predominant effects of iodoacetate should have been inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glycolysis. If this is true pyruvate should be able to diminish the effects of iodoacetate on the phosphorylase system. This was, in fact, the case as can also be noted in Table 1. The addition of 20 mM pyruvate to the incubation solution was without effect upon the response of the

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The effect of metabolic inhibitors on the response of the perfused rat heart to epinephrine

Cited by 16 publications

References 5 publications

The time‐dependent and dose‐dependent effects of caffeine on the contraction of the ferret heart

The time‐dependent and dose‐dependent effects of caffeine on the contraction of the ferret heart

Effects of calcium, sodium and potassium ions on contractility of isolated atria and their responses to noradrenaline

Metabolic Regulation of the Response of the Glycogen Phosphorylase System to Hormones in Rat Heart and Diaphragm

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