Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential.
The effects of ellagic acid, a phenolic phytochemical contained in fruits and vegetables, on sarcoplasmic reticulum Ca 2+ uptake and myocardial contraction were examined in mouse ventricular myocardia. In cardiomyocytes loaded with Fura-2 (a fluorescent Ca 2+ indicator), isoprenaline (a -adrenoceptor agonist) produced a decrease in the basal fluorescence ratio. This decrease was inhibited by propranolol (a -adrenoceptor antagonist) and cyclopiazonic acid (a sarcoplasmic reticulum Ca 2+-ATPase inhibitor). Ellagic acid produced a decrease in basal fluorescence ratio, which was completely inhibited by cyclopiazonic acid. In isolated myocardial tissue preparations, isoprenaline increased the contractile force and shortened the time required for relaxation. Ouabin, a cardiac glycoside, increased the contractile force but did not affect the time required for relaxation. Ellagic acid shortened the time required for relaxation but did not affect the contractile force. The beating rate of isolated right atria was increased by isoprenaline, but ellagic acid had no effect. In conclusion, ellagic acid accelerates sarcoplasmic reticulum Ca 2+ uptake and myocardial relaxation without affecting the contractile force or the beating rate. Ellagic acid, which has such non-conventional mode of action, may be of value in the long-term maintenance of cardiac function.
The pharmacokinetics of novel formulations of curcumin mixed with squalene (CSQU) and of curcumin mixed with docosahexaenoic acid (CDHA) was investigated and compared with a standardized unformulated curcumin extract (StdC) and a solid lipid curcumin particle (SLCP) formulation in a randomized, open-label, crossover study. Ten healthy subjects consumed a single dose of each formulation, and blood samples were collected over 8 h. Plasma concentrations of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) were measured. The dose-normalized AUC0-8h of curcumin was significantly higher for SLCP (2.2-fold), CSQU (2.3-fold) and CDHA (2.8-fold) than for StdC. The dose-normalized AUC0-8h of DMC and BDMC did not significantly change, but their Tmax was significantly shortened for SLCP, CSQU, and CDHA. In conclusion, compared to StdC, both fish oil formulations, CSQU and CDHA, significantly improved curcumin absorption as well as SLCP, and CDHA was bioequivalent or superior to SLCP. No sex differences were observed in curcumin absorption.
Myocardial intracellular Ca 2+ and membrane potential oscillations were studied in the isolated guinea-pig, rat and mouse pulmonary veins with immunohistochemical, confocal microscopic and electrophysiological analyses. The myocardial layer was present between the smooth muscle layer and the adventitia. Intracellular Ca 2+ oscillations were observed in three species, which were inhibited by ryanodine. Spontaneous Ca 2+ waves were observed to propagate along the longitudinal axis of the cell or as a spiral rotating around a subcellular core; the propagation velocity of these Ca 2+ waves was similar to that reported in atrial and ventricular cardiomyocytes. In quiescent pulmonary vein cardiomyocytes, membrane transporter inhibitors such as ouabain, tertiapin and ATX-2 induced Ca 2+ oscillations and repetitive Ca 2+ transients. Spontaneous action potentials were present in about 35%, 4% 45% of the preparations from the guinea-pig, rat and mouse respectively. In quiescent preparations from the guinea-pig, noradrenaline induced a slow depolarization of the resting membrane potential followed by constant repetitive generation of action potentials, which were inhibited by ryanodine. In quiescent preparations from the rat, noradrenaline induced an initial hyperpolarization and a subsequent depolarization of the resting membrane potential. This was followed by generation of automatic action potentials which occurred in repetitive bursts with a similar maximum diastolic potential during and between bursts. Ryanodine either abolished or reduced the duration of action-potential bursts. In quiescent preparations from the mouse, noradrenaline induced automatic electrical activity which appeared in the three waveform types; the first was a constant firing (like guinea-pig type) and the second was a repetitive burst (like rat type) and the third was also a repetitive burst but with a more negative maximum diastolic potential between the bursts than during the bursts and thus an EAD-like waveform. These results indicate that the pulmonary vein myocardium generates automatic electrical activity under adrenergic influence, which is probably triggered by intracellular Ca 2+ oscillations. The difference in firing pattern between the guinea-pig, rat and mouse may be due to the difference in hyperpolarizing mechanisms.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.