{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:04:57Z","timestamp":1792789497577,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Genoa University Fondo di Ricerca di Ateneo"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Previously, it has been shown that cortisol induces oxidative stress in human platelets, stimulating reactive oxygen species production, superoxide anion formation, lipid peroxidation, and depleting antioxidant defenses. In this study, the cortisol effect on platelet function has been described. Results demonstrate that cortisol stimulates platelet activation and aggregation, leading to CD62P surface exposure and intracellular calcium elevation. Cortisol potentiates its aggregating effect, reducing the level of the powerful anti-aggregating agent nitric oxide (NO). Likewise, cortisol reduces cGMP levels. Moreover, specific inhibitors of the Src\/Syk\/PI3K\/AKT pathways reverse the inhibiting effect of cortisol, partially restoring NO and cGMP levels. Unexpectedly, cortisol stimulates endothelial nitric oxide synthase (eNOS) activity, measured in platelet lysates prepared by whole cells treated with the hormone. The phosphorylation of the Ser1177 eNOS activating-residue is increased by cortisol. The Src\/Syk\/PI3K\/AKT pathways appear to be involved in the phosphorylation of this residue. Moreover, cortisol induces the formation of nitrotyrosine, that can be considered a biomarker for reactive nitrogen species, including peroxynitrite. In conclusion, through these mechanisms, cortisol potentiates its capacity to induce oxidative stress in human platelets.<\/jats:p>","DOI":"10.3390\/ijms26041421","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T04:44:03Z","timestamp":1739162643000},"page":"1421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Cortisol Effect on the NO\/cGMP Pathway"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5042-6614","authenticated-orcid":false,"given":"Maria Grazia","family":"Signorello","sequence":"first","affiliation":[{"name":"Biochemistry Laboratory, Department of Pharmacy, University of Genoa, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4445-7198","authenticated-orcid":false,"given":"Giuliana","family":"Leoncini","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory, Department of Pharmacy, University of Genoa, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ygcen.2013.05.022","article-title":"Importance of the glucocorticoid stress response in a changing world: Theory, hypotheses and perspectives","volume":"190","author":"Angelier","year":"2013","journal-title":"Gen. 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