Inhibiting NCX delays the early onset of Ca alternans in myocytes from spontaneously hypertensive rats (SHR).

Spontaneously hypertensive rats (SHR) are more susceptible to cardiac alternans, a precursor to arrhythmias. Ca alternans is a beat-to-beat oscillation in Ca transient amplitude at constant stimulation frequency. We previously found that the early onset of alternans in SHR hearts is associated with prolonged sarcoplasmic reticulum (SR) Ca release refractoriness, primarily influenced by SR Ca load and RyR2 sensitivity.

Prolonged Ca release refractoriness and T-tubule disruption as determinants of increased propensity to cardiac alternans in the hypertensive heart disease.

Aim: Cardiac alternans is a dynamical phenomenon linked to the genesis of severe arrhythmias and sudden cardiac death. It has been proposed that alternans is caused by alterations in Ca handling by the sarcoplasmic reticulum (SR), in both the SR Ca uptake and release processes. The hypertrophic myocardium is particularly prone to alternans, but the precise mechanisms underlying its increased vulnerability are not known.

Pharmacological inhibition of translocon is sufficient to alleviate endoplasmic reticulum stress and improve Ca handling and contractile recovery of stunned myocardium.

Introduction: The function of endoplasmic reticulum (ER), a Ca storage compartment and site of protein folding, is altered by disruption of intracellular homeostasis. Misfolded proteins accumulated in the ER lead to ER stress (ERS), unfolded protein response (UPR) activation and ER Ca loss. Myocardial stunning is a temporary contractile dysfunction, which occurs after brief ischemic periods with minimal or no cell death, being oxidative stress and Ca overload potential underlying mechanisms.

The activation of the G protein-coupled estrogen receptor (GPER) prevents and regresses cardiac hypertrophy.

Ventricular hypertrophy is a risk factors for arrhythmias, ischemia and sudden death. It involves cellular modifications leading to a pathological remodeling and is associated with heart failure. The activation of the G protein-coupled estrogen receptor (GPER) mediates beneficial actions in the cardiovascular system.