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A hallmark of hypertension is elevated total peripheral vascular resistance, often driven by sustained and abnormal vasoconstriction. Calcium ions (Ca\u00b2\u207a) 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 (IP\n                    <jats:sub>3<\/jats:sub>\n                    R) and the transient receptor potential canonical type 3 (TRPC3) channel are critical mediators of Ca\u00b2\u207a signaling. IP\n                    <jats:sub>3<\/jats:sub>\n                    R activation triggers Ca\u00b2\u207a release from the endoplasmic reticulum, while TRPC3 channels facilitate Ca\u00b2\u207a and Na\u207a influx across the plasma membrane. Several studies have shown that both IP\n                    <jats:sub>3<\/jats:sub>\n                    Rs 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 IP\n                    <jats:sub>3<\/jats:sub>\n                    R\u2013TRPC3 coupling and Ca\u00b2\u207a influx. IP\u2083 and endothelin-1 stimulate TRPC3 channels and promote their molecular coupling to IP\n                    <jats:sub>3<\/jats:sub>\n                    Rs, leading to activation of nonselective cation currents in artery myocytes. Increased expression and\/or activity of IP\n                    <jats:sub>3<\/jats:sub>\n                    Rs and TRPC3 channels amplifies this signaling, contributing to the increased vascular tone characteristic of the hypertensive state. Understanding the molecular interplay between IP\n                    <jats:sub>3<\/jats:sub>\n                    Rs and TRPC3 channels offers new insight into the dysregulated Ca\u00b2\u207a signaling underlying hypertension. Targeting this coupling mechanism may represent a novel therapeutic strategy to restore vascular homeostasis and reduce blood pressure in affected individuals.\n                  <\/jats:p>","DOI":"10.1007\/s00424-026-03175-y","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T06:00:35Z","timestamp":1777701635000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The role of IP3R and TRPC3 channels in vasoconstriction and hypertension"],"prefix":"10.1007","volume":"478","author":[{"given":"Raiana dos Anjos","family":"Moraes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quiara Lovatti","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliane Barreto","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Leonne Cruz","family":"de Jesus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dar\u00edzy Fl\u00e1via","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"3175_CR1","doi-asserted-by":"publisher","DOI":"10.4161\/sgtp.28846","volume":"5","author":"G Loirand","year":"2014","unstructured":"Loirand G, Pacaud P (2014) Involvement of Rho GTPases and their regulators in the pathogenesis of hypertension. 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