Pulmonary circulation is an important circulatory system in which the body brings in oxygen. Pulmonary arterial hypertension (PAH) is a progressive and fatal disease that predominantly affects women. Sustained pulmonary vasoconstriction, excessive pulmonary vascular remodeling, in situ thrombosis, and increased pulmonary vascular stiffness are the major causes for the elevated pulmonary vascular resistance (PVR) in patients with PAH. The elevated PVR causes an increase in afterload in the right ventricle, leading to right ventricular hypertrophy, right heart failure, and eventually death. Understanding the pathogenic mechanisms of PAH is important for developing more effective therapeutic approach for the disease. An increase in cytosolic free concentration ( ) in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and an important stimulus for PASMC migration and proliferation which lead to pulmonary vascular wall thickening and remodeling. It is thus pertinent to define the pathogenic role of signaling in pulmonary vasoconstriction and PASMC proliferation to develop new therapies for PAH. in PASMC is increased by influx through channels in the plasma membrane and by release or mobilization from the intracellular stores, such as sarcoplasmic reticulum (SR) or endoplasmic reticulum (ER). There are two entry pathways, voltage-dependent influx through voltage-dependent channels (VDCC) and voltage-independent influx through store-operated Ca2+ channels (SOC) and receptor-operated channels (ROC). This paper will focus on the potential role of VDCC, SOC, and ROC in the development and progression of sustained pulmonary vasoconstriction and excessive pulmonary vascular remodeling in PAH. 1. Introduction The only organ in the body to receive the entire cardiac output (CO) at one time is the lung. To receive a high flow of volume from the entire CO, the pulmonary circulatory system must maintain a low-resistance and low-pressure system to carry blood to the pulmonary capillaries. Deoxygenated venous blood flows through the pulmonary artery to the pulmonary capillaries where oxygen and carbon dioxide gas exchange occurs. Pulmonary hypertension (PH) is a severe chronic disorder that affects the pulmonary circulatory system. This disorder is often a deadly hemodynamic irregularity that may be idiopathic, heritable, or secondary to other diseases such as chronic obstructive pulmonary disease (COPD). Pulmonary arteries are thin and have low myogenic tone compared to systemic arteries. Therefore, pulmonary arteries rely on
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