Comparison of the mechanisms underlying the positive inotropic actions of dopamine, adrenaline and isoprenaline on the isolated rabbit papillary muscle

Hj, Schümann; Motomura, Shigeru; Endoh, Masao; Brodde, O.‐E.

doi:10.1007/bf00509270

Cited by 30 publications

(8 citation statements)

References 20 publications

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“…Dopa mine has a positive inotropic effect on the myocardium [4. 15, 24] which depends upon the contraction frequency [25] and is more pronounced than the positive chronotropic effect on the sino-atrial node [ 15], A develop mental trend toward the characteristic effects of dopamine in the adult was apparent in the present study on developing swine ( fig. 1, 2; table II-IV).…”

Section: Discussionmentioning

confidence: 65%

Cardiovascular Effects of Dopamine in Developing Swine

Buckley¹,

Brazeau²,

Frasier³

1983

Neonatology

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Cardiac function and peripheral blood flows were measured before and during single intravenous injections of dopamine (2–25 μg/kg) in developing and mature swine anesthetized with pentobarbital. A positive inotropic effect was observed in even the youngest swine. Renal vasoconstriction was observed even after low doses of dopamine in animals younger than 1 month of age, and femoral vasoconstriction in animals younger than 2 weeks of age, unless α-adrenergic receptors were blocked by phentolamine. We concluded that the vasodilator responses to dopamine are slower to develop in the renal than in the femoral circulation.

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Section: Discussionmentioning

confidence: 65%

Cardiovascular Effects of Dopamine in Developing Swine

Buckley¹,

Brazeau²,

Frasier³

1983

Neonatology

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“…The time course as well as the maximum of this increase was nearly identical with that obtainable with an equieffective concentration; that is, the ECBo for the positive inotropic effect of adrenaline (Schiimann et al, 1977) or isoprenaline (Schumann et al, 1975(Schumann et al, , 1977Endoh, Brodde & Schiimann, 1975). An equivalent concentration of dopamine, on the contrary, produced only an approximately 50% increase of the cyclic AMP level of the rabbit papillary muscle (Schumann et al, 1977).…”

Section: Discussionmentioning

confidence: 76%

Studies on the mechanism of the positive inotropic action evoked by epinine on the rabbit isolated papillary muscle at different rates of beating

Brodde¹,

Motomura²,

Schümann³

1979

Clin Exp Pharmacol Physiol

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1. Effects of epinine on cyclic AMP and contractility were investigated in rabbit papillary muscles driven at a rate of 0.5 or 2.0 Hz. 2. When the frequency of stimulation was increased from 0.5 to 2.0 Hz, the log dose-response curve for the positive inotropic effect of epinine was displaced to the left, whereas the maximum of the developed tension was not changed. 3. At both frequencies phentolamine (1 mumol/l) shifted the lower part of the log dose-response curve for epinine to the right, whereas pindolol (30 nmol/l) affected mainly the upper part. In the presence of both alpha- and beta-adrenoceptor antagonists, the whole curve was shifted to the right in a parallel manner. However, cocaine (30 mumol/l) did not significantly influence the log dose-response curve of epinine. 4. At 0.5 Hz a submaximal effective concentration of epinine (100 mumol/l) led to an approximately 100% increase of the cyclic AMP level after 60s; the same increase of the cyclic AMP level was induced at 2.0 Hz by one-third the concentration of epinine (30 mumol/l). 5. Phentolamine (1 mumol/l) did not affect the increase of the cyclic AMP level evoked by epinine, whereas pindolol (30 nmol/l) completely depressed it. 6. The present results indicate that epinine produces its positive inotropic effect through direct stimulation of myocardial alpha-adrenoceptors as well as beta-adrenoceptors, depending upon the concentration: in lower concentrations it acts mainly on alpha-adrenoceptors, whereas in higher concentrations it acts predominantly on beta-adrenoceptors. The positive inotropic effect through beta-adrenoceptor stimulation is mediated by cyclic AMP, while that through alpha-adrenoceptors is not.

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“…In addition, it has been shown that other functional proteins such as myosin binding protein C and NCX are phosphorylated to potentially contribute to the regulation of Ca 2+ handling (11,12). Most sympathomimetic amines such as phenylephrine (20,23,24), dopamine (21,46), norepinephrine, epinephrine (46), isoproterenol (22), dobutamine (25), and denopamine (26) ] o (9). This may be partly due to a decrease in myofilament Ca 2+ sensitivity in relation to troponin I phosphorylation and abbreviation of Ca 2+ transients due to activation of SERCA2a.…”

Section: -1 β-Adrenoceptor Stimulationmentioning

confidence: 99%

Signal Transduction and Ca2+ Signaling in Intact Myocardium

Endoh

2006

J Pharmacol Sci

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Abstract. The experimental procedures to simultaneously detect contractile activity and Ca 2+transients by means of the Ca 2+ sensitive bioluminescent protein aequorin in multicellular preparations, and the fluorescent dye indo-1 in single myocytes, provide powerful tools to differentiate the regulatory mechanisms of intrinsic and external inotropic interventions in intact cardiac muscle. The regulatory process of cardiac excitation-contraction coupling is classified into three categories; upstream (Ca 2+ mobilization), central (Ca 2+ binding to troponin C), and / or downstream (thin filament regulation of troponin C property or crossbridge cycling and crossbridge cycling activity itself) mechanisms. While a marked increase in contractile activity by the Frank-Starling mechanism is associated with only a small alteration in Ca 2+ transients (downstream mechanism), the force-frequency relationship is primarily due to a frequencydependent increase of Ca 2+ transients (upstream mechanism) in mammalian ventricular myocardium. The characteristics of regulation induced by β-and α-adrenoceptor stimulation are very different between the two mechanisms: the former is associated with a pronounced facilitation of an upstream mechanism, whereas the latter is primarily due to modulation of central and / or downstream mechanisms. α-Adrenoceptor-mediated contractile regulation is mimicked by endothelin ET A -and angiotensin II AT 1 -receptor stimulation. Acidosis markedly suppresses the regulation induced by Ca 2+ mobilizers, but certain Ca 2+ sensitizers are able to induce the positive inotropic effect with central and / or downstream mechanisms even under pathophysiological conditions.

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Comparison of the mechanisms underlying the positive inotropic actions of dopamine, adrenaline and isoprenaline on the isolated rabbit papillary muscle

Cited by 30 publications

References 20 publications

Cardiovascular Effects of Dopamine in Developing Swine

Cardiovascular Effects of Dopamine in Developing Swine

Studies on the mechanism of the positive inotropic action evoked by epinine on the rabbit isolated papillary muscle at different rates of beating

Signal Transduction and Ca2+ Signaling in Intact Myocardium

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