Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels

Abstract

Cardiac hypertrophy is a thickening of the heart muscle that is associated with cardiovascular diseases such as hypertension and myocardial infarction. It occurs initially as an adaptive process against increased workloads and often leads to sudden arrhythmic deaths. Studies suggest that the lethal arrhythmia is attributed to hypertrophy-induced destabilization of cardiac electrical activity, especially the prolongation of the action potential. The reduced activity of I is demonstrated to be responsible for the ionic mechanism of prolonged action potential duration and arrhythmogeneity. Isosteviol (STV), a derivative of stevioside, plays a protective role in a variety of stress-induced cardiac diseases. Here we report effects of STV on rat ISO-induced hypertrophic cardiomyocytes. STV alleviated ISO-induced hypertrophy of cardiomyocytes by decreasing cell area of hypertrophied cardiomyocytes. STV application prevented the prolongation of action potential which was prominent in hypertrophied cells. The decrease and increase of current densities for I and I observed in hypertrophied myocytes were both prevented by STV application. In addition, the results of qRT-PCR suggested that the changes of electrophysiological activity of I and I are correlated to the alterations of the mRNA transcription level.

Dihydropyridines as Calcium Channel Blockers: An Overview

“…Nifedipine may possibly meet the requirements of being a selective antagonist by exerting its best effect on the vessels compared to the myocardium, and also has no (or very little) effect on nodal tissue or atrioventricular conduction; The problem is that its selectivity for vessels is associated with rapid uptake and plasma distribution, as well as a rapid rate of fixation to its "receptor" in the complex of the calcium ion channel, for this reason produces rapid peripheral vasodilation. As a consequence, the autonomic nervous system is stimulated, determining a rapid and significant increase of the heart rate, which forces to concomitant treatment with β-blocker or a preparation of prolonged release [24][25][26][27][28][29].…”

Acute effect of thymoquinone on action potential and ionic currents of rat cardiac myocytes

“…Hence, despite the opposite effects of these currents, prolongation was eventually measured in the APD. These results seem to be interesting for a substance that is claimed to be benefi cial for diseases such as diabetes, pathological hypertrophy and heart failure characterized by prolonged APD (3,16,26,27). The fi ndings of this study imply that TQ may aggravate the risk of pathological events in certain cardiovascular diseases.…”

Erythrocyte Partitioning Profile of Isosteviol in Human and Rat Blood

“…This will be needed to inform on likely drug-displacement interactions at protein levels that have been reported for similar anionic drugs like salicylates, phenylbutazone, and indomethacin 12, 13. Further, the likely future trial of isosteviol as a therapeutic agent to address cardiac hypertrophy 2 will probably require its modeled administration over a period of time. This will often require that toxicity arising from drug-displacement interactions, in likely instances of its potential coadministration with other interventions, is adequately considered.…”

“…Isosteviol is a synthetic derivative of steviol glycosides that has been the focus of several studies in recent times owing to pharmacologic effects associated with it. Neuroprotective attributes in cerebral ischemia model 1 and the attenuation of action potential in hypertrophied cardiomyocytes 2 are some major findings of potential clinical significance that have been reported recently. Although these properties have also been associated with steviol glycosides, 3 a combination of poor intestinal absorption, extensive metabolism, 4 and a much-debated genotoxicity 5 limits the therapeutic usefulness of isosteviol's glycosides.…”

“…Although these properties have also been associated with steviol glycosides, 3 a combination of poor intestinal absorption, extensive metabolism, 4 and a much-debated genotoxicity 5 limits the therapeutic usefulness of isosteviol's glycosides. Preliminary studies with isosteviol suggest promising benefits because of its reasonable absorption 6 with no documented genotoxicity issues previously associated with steviol glycosides 2 …”