Gingerol, isoproterenol and ouabain normalize impaired post-rest behavior but not force–frequency relation in failing human myocardium

Abstract

Inotropic interventions that stimulate SR Ca(2+)-ATPase or inhibit Na+/Ca(2+)-exchange normalize impaired post-rest behavior. Force-frequency behavior is only slightly improved by stimulation of SR Ca(2+)-ATPase but not by inhibition of Na+/Ca(2+)-exchange. This dissociation between post-rest and force-frequency behavior results from diastolic dysfunction at high stimulation rates.

Increased SR Ca cycling contributes to improved contractile performance in SERCA2a-overexpressing transgenic rats

“…The present data also agree with our observations in failing human myocardium that the FFR may be improved by low concentrations of forskolin [30] or isoproterenol [31]. However, stimulation of the cAMP-PKA axis not only stimulates SERCA2a activity by PLB phosphorylation, but has multiple further effects such as phosphorylation of LTCC, ryanodine receptors (RyR), or troponin C. Therefore, in our previous studies stimulation of the cAMP -PKA axis was far from normalizing contractility, and higher concentrations of forskolin or isoproterenol even had detrimental effects related to Ca 2+ overload.…”

“…Nevertheless, increased SERCA2a protein expression results in more effective SR Ca 2+ reloading during rest. Similarly we could recently show that positive inotropic compounds which stimulate SERCA2a can improve the impaired post-rest behavior in failing human myocardium [31].…”

Gingerols and shogaols: Important nutraceutical principles from ginger

“…A study by Maier et al (2000) indicated that 10-GN, at 0.1 lmol/L, also exerts a positive inotropic effect by increasing sarcoplasmic reticulum Ca 2+ uptake in human myocardial homogenates. The maximum contraction response, induced by PGF(2a) in the presence of intact vascular endothelium, was achieved in mouse mesenteric veins, following treatment with 0.3 mM (±)-6-GN (Hata et al, 1998).…”

Remodelamento miocárdico após grandes infartos converte potenciação pós-pausa em decaimento da força em ratos

“…On the other hand, the inhibition of transsarcolemmal Ca 2+ extrusion by NCX in our preparations (by using Li + ) enhanced the potentiation of C muscles, which confirms the importance of Ca 2+ efflux mechanisms to negatively modulate the PRC of rat LV muscle 6,7 . Indeed, it was reported that the stimulation of NCX leads to an increasing Ca 2+ efflux and Na + influx, and consequently, a depression of the PRC 27,28 .…”

“…The literature is controversial concerning the behavior of PRC in post-MI remodeling. In human failing myocardium, authors reported either depressed potentiation 32,33 or decay 28 of contraction after prolonged pauses. In animal models 9,10 , depressed potentiation compared to controls were reported from infarcted rats.…”