{"p"=>{"__content__"=>"Hypertension is a major global health concern and a leading risk factor for cardiovascular diseases, including stroke, myocardial infarction, and heart failure. A hallmark of hypertension is elevated total peripheral vascular resistance, often driven by sustained and abnormal vasoconstriction. Calcium ions (Ca²⁺) play a central role in vascular smooth muscle cell (VSMC) contraction, and their intracellular concentration is tightly regulated by multiple signaling pathways. Among these, the inositol 1,4,5-trisphosphate receptor (IPR) and the transient receptor potential canonical type 3 (TRPC3) channel are critical mediators of Ca²⁺ signaling. IPR activation triggers Ca²⁺ release from the endoplasmic reticulum, while TRPC3 channels facilitate Ca²⁺ and Na⁺ influx across the plasma membrane. Several studies have shown that both IPRs and TRPC3 channels are upregulated in hypertensive animal models. Human studies have also demonstrated elevated TRPC3 expression in the context of pulmonary arterial hypertension (PAH). This review provides a comprehensive overview of the structural domains and membrane microdomains that facilitate IPR–TRPC3 coupling and Ca²⁺ influx. IP₃ and endothelin-1 stimulate TRPC3 channels and promote their molecular coupling to IPRs, leading to activation of nonselective cation currents in artery myocytes. Increased expression and/or activity of IPRs and TRPC3 channels amplifies this signaling, contributing to the increased vascular tone characteristic of the hypertensive state. Understanding the molecular interplay between IPRs and TRPC3 channels offers new insight into the dysregulated Ca²⁺ signaling underlying hypertension. Targeting this coupling mechanism may represent a novel therapeutic strategy to restore vascular homeostasis and reduce blood pressure in affected individuals.", "sub"=>[{"__content__"=>"3"}, {"__content__"=>"3"}, {"__content__"=>"3"}, {"__content__"=>"3"}, {"__content__"=>"3"}, {"__content__"=>"3"}, {"__content__"=>"3"}]}}