{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:06:50Z","timestamp":1792638410286,"version":"4.5.0"},"reference-count":40,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ZIA ES103353-03"],"award-info":[{"award-number":["ZIA ES103353-03"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"British Heart Foundation Centre of Excellence","award":["RE\/18\/6\/34217"],"award-info":[{"award-number":["RE\/18\/6\/34217"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dihydropyridines such as amlodipine are widely used as antihypertensive agents, being prescribed to \u223c70 million Americans and &amp;gt;0.4 billion adults worldwide. Dihydropyridines block voltage-gated Ca2+ channels in resistance vessels, leading to vasodilation and a reduction in blood pressure. Various meta-analyses show that dihydropyridines are relatively safe and effective in reducing hypertension. The use of dihydropyridines has recently been called into question as these drugs appear to activate store-operated Ca2+ entry in fura-2-loaded nonexcitable cells, trigger vascular remodeling, and increase heart failure, leading to the questioning of their clinical use. Given that hypertension is the dominant \u201csilent killer\u201d across the globe affecting \u223c1.13 billion people, removal of Ca2+ channel blockers as antihypertensive agents has major health implications. Here, we show that amlodipine has marked intrinsic fluorescence, which further increases considerably inside cells over an identical excitation spectrum as fura-2, confounding the ability to measure cytosolic Ca2+. Using longer wavelength Ca2+ indicators, we find that concentrations of Ca2+ channel blockers that match therapeutic levels in serum of patients do not activate store-operated Ca2+ entry. Antihypertensive Ca2+ channel blockers at pharmacological concentrations either have no effect on store-operated channels, activate them indirectly through store depletion or inhibit the channels. Importantly, a meta-analysis of published clinical trials and a prospective real-world analysis of patients prescribed single antihypertensive agents for 6\u2009mo and followed up 1\u2009yr later both show that dihydropyridines are not associated with increased heart failure or other cardiovascular disorders. Removal of dihydropyridines for treatment of hypertension cannot therefore be recommended.<\/jats:p>","DOI":"10.1093\/function\/zqad047","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T17:27:31Z","timestamp":1695058051000},"source":"Crossref","is-referenced-by-count":7,"title":["A Reappraisal of the Effects of L-type Ca2+ Channel Blockers on Store-Operated Ca2+ Entry and Heart Failure"],"prefix":"10.1152","volume":"4","author":[{"given":"Gary S","family":"Bird","sequence":"first","affiliation":[{"name":"Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH , Research Triangle Park, NC 27709 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7214-6951","authenticated-orcid":false,"given":"Diane","family":"D\u2019Agostin","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH , Research Triangle Park, NC 27709 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6453-754X","authenticated-orcid":false,"given":"Safaa","family":"Alsanosi","sequence":"additional","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow , Glasgow G12 8TA , UK"},{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al Qura University , P.O. 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