This results in higher cardiac contractility and an increase in cardiac vagal tone. Nitric oxide also acts on cardiac muscle to decrease contractility and heart rate. PDE3 enzymes are involved in regulation of cardiac and vascular smooth muscle contractility. Fetal heart rate decreases due to spontaneous deceleration due to direct depression of cardiac contractility. Aged apelin knockout mice develop progressive impairment of cardiac contractility. This leads to an increase in cytoplasmic calcium concentration, which improves cardiac contractility. Effects on cardiac contractility and stroke volume are insignificant. Increased end systolic volume is usually caused by reduced contractility. The activated stellate cell is characterized by proliferation, contractility, and chemotaxis. NO contributes to the regulation of cardiac contractility. It also upregulates the thick filament protein myosin, which helps to increase contractility. Some individuals may also have a decrease in cardiac contractility. This increase in calcium influx results in increased contractility. Lat-A-induces reduction of actomyosin contractility. This impaired contractility occurs through a number of mechanisms.