Abstract
Periplocymarin, which belongs to cardiac glycosides, is an effective component extracted from Periplocae Cortex. However, its cardiovascular effects remain unidentified. In the present study, injection of periplocymarin (5 mg/kg) through external jugular vein immediately increased the mean arterial pressure (MAP) in anesthetized C57BL/6 mice. Ex vivo experiments using mouse mesenteric artery rings were conducted to validate the role of periplocymarin on blood vessels. However, periplocymarin failed to induce vasoconstriction directly, and had no effects on vasoconstriction induced by phenylephrine (Phe) and angiotensin II (Ang II). In addition, vasodilatation induced by acetylcholine (Ach) was insusceptible to periplocymarin. Echocardiography was used to evaluate the effects of periplocymarin on cardiac function. The results showed that the injection of periplocymarin significantly increase the ejection fraction (EF) in mice without changing the heart rate. In vitro studies using isolated neonatal rat ventricular myocytes (NRVMs) revealed that periplocymarin transiently increased the intracellular Ca2+ concentration observed by confocal microscope. But in Ca2+-free buffer, this phenomenon vanished. Besides, inhibition of sodium potassium-activated adenosine triphosphatase (Na+-K+-ATPase) by digoxin significantly suppressed the increase of MAP and EF in mice, and the influx of Ca2+ in cardiomyocytes, mediated by periplocymarin. Collectively, these findings demonstrated that periplocymarin increased the contractility of myocardium by promoting the Ca2+ influx of cardiomyocytes via targeting on Na+-K+-ATPase, which indirectly led to the instantaneous rise of blood pressure.
Highlights
Cardiovascular diseases (CVDs) are the most common causes of death worldwide
In order to explore the cardiotonic mechanism of periplocymarin, we examined the effect of periplocymarin on intracellular Ca2+ levels in isolated neonatal rat ventricular myocytes (NRVMs)
Periplocae Cortex has a long history as traditional Chinese medicine (TCM) for the treatment of autoimmune diseases (Guo et al, 2013)
Summary
Cardiovascular diseases (CVDs) are the most common causes of death worldwide. CVDs are disorders of the heart and blood vessels, including heart failure (HF), hypertension, and other conditions (Tzoulaki et al, 2016; Zhao et al, 2019). Cardiac glycosides, including digoxin and ouabain, exhibit high selectivity to heart and exert a positive inotropic action by enhancing myocardial contractility and improve cardiac pumping function (Alogna et al, 2016). They convey vitally important effects as therapeutic agents for the treatment of HF. Endogenous cardiotonic ouabain can alter intracellular calcium (Ca2+) homeostasis in smooth muscle cells, and affect the constriction of vessels, eventually resulting in approximately 30% increase in systolic blood pressure in rodent model after 1 week of ouabain treatment (Pulgar et al, 2013; Zulian et al, 2013). Digoxin has no effect on cytolic free Ca2+ concentration in vascular smooth muscle cells and does not alter blood pressure (Zulian et al, 2013)
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