continuous-arterial-pressure-monitoring-conscious-rodents-using

Continuous Arterial Pressure Monitoring in Conscious Rodents Using Implantable Telemetry and Comparison with the Tail-Cuff Method

Radio telemetry enables reliable, continuous arterial blood pressure (BP) monitoring in conscious rodents under physiological conditions, while minimizing ...

isolating-ventricular-cardiomyocytes-from-mouse-model-doxorubicin

Isolating Ventricular Cardiomyocytes from a Mouse Model of Doxorubicin Cardiotoxicity

Doxorubicin (DOX) is an effective chemotherapeutic drug whose clinical application is limited by progressive, dose-dependent cardiotoxicity that ...

Dalian Medical University

xi'an jiaotong university

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.  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.  studies using isolated neonatal rat ventricular myocytes (NRVMs) revealed that periplocymarin transiently increased the intracellular Ca concentration observed by confocal microscope. But in Ca-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 Ca in cardiomyocytes, mediated by periplocymarin. Collectively, these findings demonstrated that periplocymarin increased the contractility of myocardium by promoting the Ca influx of cardiomyocytes  targeting on Na-K-ATPase, which indirectly led to the instantaneous rise of blood pressure.

Periplocymarin Plays an Efficacious Cardiotonic Role  Promoting Calcium Influx.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new antidiabetic drugs that reduce hyperglycemia by inhibiting the glucose reabsorption in renal proximal tubules. Clinical studies have shown that SGLT2 inhibitors not only improve glycemic control but also reduce major adverse cardiovascular events (MACE, cardiovascular and total mortality, fatal or nonfatal myocardial infarction or stroke) and hospitalization for heart failure (HF), and improve outcome in chronic kidney disease. These cardiovascular and renal benefits have now been confirmed in both diabetes and non-diabetes patients. The precise mechanism(s) responsible for the protective effects are under intensive investigation. This review examines current evidence on the cardiovascular benefits of SGLT2 inhibitors, with a special emphasis on the vascular actions and their potential mechanisms.

Sodium-Glucose Cotransporter-2 Inhibitors in Vascular Biology: Cellular and Molecular Mechanisms.

Drug-induced liver injury (DILI), especially acetaminophen overdose, is the leading cause of acute liver failure. Pregnane X receptor (PXR) is a nuclear receptor and the master regulator of drug metabolism. Aberrant activation of PXR plays a pathogenic role in the acetaminophen hepatotoxicity. Here, we aimed to examine the S-nitrosylation of PXR (SNO-PXR) in response to acetaminophen. We found that PXR was S-nitrosylated in hepatocytes and the mouse livers after exposure to acetaminophen or S-nitrosoglutathione (GSNO). Mass spectrometry and site-directed mutagenesis identified the cysteine 307 as the primary residue for S-nitrosylation (SNO) modification. In hepatocytes, SNO suppressed both agonist-induced (rifampicin and SR12813) and constitutively active PXR (VP-PXR, a human PXR fused to the minimal transactivator domain of the herpes virus transcription factor VP16) activations. Furthermore, in acetaminophen-overdosed mouse livers, PXR protein was decreased at the centrilobular regions overlapping with increased SNO. In PXR-/- mice, replenishing the livers with the SNO-deficient PXR significantly aggravated hepatic necrosis, increased HMGB1 release, and exacerbated liver injury and inflammation. Particularly, we demonstrated that S-nitrosoglutathione reductase (GSNOR) inhibitor N6022 promoted hepatoprotection by increasing the levels of SNO-PXR. In conclusion, PXR is posttranslationally modified by SNO in hepatocytes in response to acetaminophen. This modification mitigated the acetaminophen-induced PXR hyperactivity. It may serve as a target for therapeutical intervention.

ArticleTotal : 2	Year
Publication title	2025
Publication title	2026

Article	Year
Periplocymarin Plays an Efficacious Cardiotonic Role Promoting Calcium Influx. Frontiers in pharmacology\| PubMed ID: 32973521	2020
Sodium-Glucose Cotransporter-2 Inhibitors in Vascular Biology: Cellular and Molecular Mechanisms. Cardiovascular drugs and therapy\| PubMed ID: 34273091	2021
S-nitrosylation attenuates pregnane X receptor hyperactivity and acetaminophen-induced liver injury. JCI insight\| PubMed ID: 38032737	2024

Yanyan Cheng

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