ArticleCirculation research2013
Dihydropyridine Ca(2+) channel blockers increase cytosolic [Ca(2+)] by activating Ca(2+)-sensing receptors in pulmonary arterial smooth muscle cells.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- The CaInternational journal of molecular sciences · 2026Article
- The Potential Role of Calcium Channels in Pulmonary Hypertension.BioMed research international · 2026Review
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Role of the calcium-sensing receptor in regulating vascular function.Journal of cell communication and signaling · 2025Review
- Growth factors involved in vascular remodeling in pulmonary arterial hypertension.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2025Review
- Up-regulated expression of two-pore domain KFrontiers in cardiovascular medicine · 2024Article
- Elucidating VSMC phenotypic transition mechanisms to bridge insights into cardiovascular disease implications.Frontiers in cardiovascular medicine · 2024Review
- Sodium-Glucose Cotransporter 2 Inhibitor Canagliflozin Antagonizes Salt-Sensitive Hypertension Through Modifying Transient Receptor Potential Channels 3 Mediated Vascular Calcium Handling.Journal of the American Heart Association · 2022Article
- Effect of Dihydropyridine Calcium Channel Blocker on Mortality of Hypertension Patients With Moderate-Severe Pulmonary Acute Respiratory Distress Syndrome: A Multicenter Retrospective Observational Cohort Study.Critical care explorations · 2021Article
- Calcium-sensing receptor in the development and treatment of pulmonary hypertension.Molecular biology reports · 2021Review
- Calcilytic NPS2143 promotes proliferation and inhibits apoptosis of spontaneously hypertensive rat vascular smooth muscle cells via activation of the renin-angiotensin system.Experimental and therapeutic medicine · 2020Article
- Upregulation of airway smooth muscle calcium-sensing receptor by low-molecular-weight hyaluronan.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Calcimimetic R568 improved cardiac remodeling by classic and novel renin-angiotensin system in spontaneously hypertensive rats.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- The Antihypertensive Drug Nifedipine Modulates the Metabolism of Chondrocytes and Human Bone Marrow-Derived Mesenchymal Stem Cells.Frontiers in endocrinology · 2019Article
- Calcium-Sensing Receptor Is Functionally Expressed in the Cochlear Perilymphatic Compartment and Essential for Hearing.Frontiers in molecular neuroscience · 2019Article
- Hypoxia selectively upregulates cation channels and increases cytosolic [CaAmerican journal of physiology. Cell physiology · 2018Article
- Article
- Distinct Effects of CaInternational journal of biological sciences · 2017Article
- The calcilytics Calhex-231 and NPS 2143 and the calcimimetic Calindol reduce vascular reactivity via inhibition of voltage-gated CaEuropean journal of pharmacology · 2016Article
- Critical Genomic Networks and Vasoreactive Variants in Idiopathic Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2016Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleAn increase in cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and an important stimulus for PASMC proliferation and pulmonary vascular remodeling. The dihydropyridine Ca(2+) channel blockers, such as nifedipine, have been used for treatment of idiopathic pulmonary arterial hypertension (IPAH).
objectiveOur previous study demonstrated that the Ca(2+)-sensing receptor (CaSR) was upregulated and the extracellular Ca(2+)-induced increase in [Ca(2+)](cyt) was enhanced in PASMC from patients with IPAH and animals with experimental pulmonary hypertension. Here, we report that the dihydropyridines (eg, nifedipine) increase [Ca(2+)](cyt) by activating CaSR in PASMC from IPAH patients (in which CaSR is upregulated), but not in normal PASMC. METHODS AND
resultsThe nifedipine-mediated increase in [Ca(2+)](cyt) in IPAH-PASMC was concentration dependent with a half maximal effective concentration of 0.20 µmol/L. Knockdown of CaSR with siRNA in IPAH-PASMC significantly inhibited the nifedipine-induced increase in [Ca(2+)](cyt), whereas overexpression of CaSR in normal PASMC conferred the nifedipine-induced rise in [Ca(2+)](cyt). Other dihydropyridines, nicardipine and Bay K8644, had similar augmenting effects on the CaSR-mediated increase in [Ca(2+)](cyt) in IPAH-PASMC; however, the nondihydropyridine blockers, such as diltiazem and verapamil, had no effect on the CaSR-mediated rise in [Ca(2+)](cyt).
conclusionsThe dihydropyridine derivatives increase [Ca(2+)](cyt) by potentiating the activity of CaSR in PASMC independently of their blocking (or activating) effect on Ca(2+) channels; therefore, it is possible that the use of dihydropyridine Ca(2+) channel blockers (eg, nifedipine) to treat IPAH patients with upregulated CaSR in PASMC may exacerbate pulmonary hypertension.
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