Does mechanical stimulation and stretch-activated ion channel blockade affect cardiomyocyte stiffness and intracellular calcium transients in spontaneously hypertensive rats?
Hypertension increases ventricular myocyte stiffness and hypersensitivity of calcium flow to mechanical stimuli via stretch-activated ion channels, providing a mechanism for hypertension-induced tachyarrhythmias.
Patients with long-lasting hypertension often suffer from atrial or ventricular arrhythmias. Evidence suggests that mechanical stimulation can change the refractory period and dispersion of the ventricular myocyte action potential through stretch-activated ion channels (SACs) and influence cellular calcium transients, thus increasing susceptibility to ventricular arrhythmias. However, the specific pathogenesis of hypertension-induced arrhythmias is unknown. In this study, through clinical data, we found that a short-term increase in blood pressure leads to a rise in tachyarrhythmias in patients with clinical hypertension. We investigated the mechanism of this phenomenon using a combined imaging system(AC) of atomic force microscopy (AFM) and laser scanning confocal microscopy. After mechanical distraction to stimulate ventricular myocytes isolated from Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), we synchronously monitored cardiomyocyte stiffness and intracellular calcium changes. This method can reasonably simulate cardiomyocytes' mechanics and ion changes when blood pressure rises rapidly. Our results indicated that the stiffness value of cardiomyocytes in SHR was significantly more extensive than that of normal controls, and cardiomyocytes were more sensitive to mechanical stress; In addition, intracellular calcium increased rapidly and briefly in rats with spontaneous hypertension. After intervention with streptomycin, a SAC blocker, ventricular myocytes are significantly less sensitive to mechanical stimuli. Thus, SAC is involved in developing and maintaining ventricular arrhythmias induced by hypertension. The increased stiffness of ventricular myocytes caused by hypertension leads to hypersensitivity of cellular calcium flow to mechanical stimuli is one of the mechanisms that cause arrhythmias. The AC system is a new research method to study the mechanical properties of cardiomyocytes. This study provides new techniques and ideas for developing new anti-arrhythmic drugs. HIGHLIGHT: The mechanism of hypertension-induced tachyarrhythmia is not precise. Through this study, it is found that the biophysical properties of myocardial abnormalities, the myocardium is excessively sensitive to mechanical stimulation, and the calcium flow appears to transient explosive changes, leading to tachyarrhythmia.
He et al. (Sun,) studied this question.