The Modulation of Cardiac Contractile Function by the Pharmacological and Toxicological Effects of Urocortin2

Toxicological Sciences : an Official Journal of the Society of Toxicology
Si ChenJi Li

Abstract

Urocortin2 (Ucn2) has been revealed to enhance cardiac function in heart failure. However, the pharmacological and toxicological effects of Ucn2 on cardiomyocytes are incompletely understood. In this study, we investigated the possible mechanisms of Ucn2 on mediating the contractility of cardiomyocytes. Mechanical properties and intracellular Ca(2+) properties were measured in isolated cardiomyocytes from different treatment groups. The stress signaling was evaluated using Western blot. The results demonstrated that Ucn2 induced maximal velocity of shortening (+dL/dt), peak height, peak shortening (PS) amplitude, maximal velocity of relengthening (-dL/dt), accompanied by a significant rise in intracellular Ca(2+) level and a fall of the mean time constant of Ca(2+) transient decay (Tau) in WT cardiomyocytes. However, these effects were abolished by preincubation of type 2 CRF receptors (CRFR2) antagonist anti-sauvagine 30 (a-SVG-30). We also found that Ucn2 treatment activated the AMPK pathway in isolated cardiomyocytes via CRFR2. Furthermore, Ucn2 induced protein kinase A (PKA) and phospholamban (PLN) phosphorylation. Pretreatment of PKA inhibitor H89 reduced the inotropic and lusitropic effects of Ucn2 as well as decreased th...Continue Reading

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Citations

Oct 30, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Xuan LiJi Li
Sep 13, 2019·Cardiovascular Drugs and Therapy·Cláudia Monteiro-PintoCarmen Brás-Silva
Sep 4, 2018·JACC. Basic to Translational Science·Laurel A GrisantiWalter J Koch
Aug 6, 2021·Journal of Cardiovascular Pharmacology and Therapeutics·Sergey V PopovLeonid N Maslov

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