{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:16:52Z","timestamp":1760149012346,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Fundacion Seneca and Campus Mare Nostrum of the Universidad de Murcia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Introduction: Previously, we found that intracellular calcium (Ca2+) homeostasis is altered in platelets from an experimental model of liver cirrhosis, namely the bile-duct-ligated (BDL) rat. These alterations are compatible with the existence of a hypercoagulable state. Objective: In the present study, we analyzed the role of nitric oxide in the abnormal calcium signaling responses of an experimental cirrhosis model, the bile duct-ligated rat. Methods: Chronic treatment with L-NAME was used to inhibit NO production in a group of control and BDL animals, and the responses compared to those obtained in a control and BDL untreated group (n = 6 each). The experiments were conducted on isolated platelets loaded with fura-2, using fluorescence spectrometry. Results: Chronic treatment with L-NAME increased thrombin-induced Ca2+ release from internal stores in both control and BDL rats. However, the effect was significantly greater in the BDL rats (p &lt; 0.05). Thrombin-induced calcium entry from the extracellular space was also elevated but at lower doses and, similarly in both control and BDL platelets, treated with the NO synthesis inhibitor. Capacitative calcium entry was also enhanced in the control platelets but not in platelets from BDL rats treated with L-NAME. Total calcium in intracellular stores was elevated in untreated platelets from BDL rats, and L-NAME pretreatment significantly (p &lt; 0.05) elevated these values both in controls and in BDL but significantly more in the BDL rats (p &lt; 0.05). Conclusions: Our results suggest that nitric oxide plays a role in the abnormal calcium signaling responses observed in platelets from BDL rats by interfering with the mechanism that releases calcium from the internal stores.<\/jats:p>","DOI":"10.3390\/ijms241310948","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T16:06:37Z","timestamp":1688141197000},"page":"10948","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of Nitric Oxide in the Altered Calcium Homeostasis of Platelets from Rats with Biliary Cirrhosis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3691-9591","authenticated-orcid":false,"given":"Masoud","family":"Akbari Aghdam","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Universidad de Murcia, 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Romec\u00edn","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Universidad de Murcia, 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7243-0240","authenticated-orcid":false,"given":"Joaqu\u00edn","family":"Garc\u00eda-Esta\u00f1","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Universidad de Murcia, 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4667-3270","authenticated-orcid":false,"given":"Noem\u00ed M.","family":"Atucha","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Medicina, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Universidad de Murcia, 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/S0168-8278(97)80420-5","article-title":"Hypercoagulability in patients with primary biliary cirrhosis and primary sclerosis cholangitis evaluated by thrombelastography","volume":"26","author":"Panagou","year":"1997","journal-title":"J. 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