{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T04:16:18Z","timestamp":1751516178755,"version":"3.41.0"},"reference-count":26,"publisher":"Canadian Science Publishing","issue":"4","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:p> Systemic infusion of nitric oxide synthase (NOS) inhibitors increases peripheral vascular resistance due to inhibition of endothelial NOS leading to the activation of the arterial baroreceptor mechanisms and inhibition of central sympathetic outflow. In the current study, we explored that systemic NOS blockage activates protein kinase A (PKA)-mediated signaling pathway through maintained cGMP-dependent protein kinase (PKG) activation. Rats were treated with 3 different concentrations of N(\u03c9)-nitro-l-arginine methyl ester (L-NAME) for 14 days. Systemic L-NAME treatment induced a dose-dependent increase in blood pressure and increased mRNA levels of atrial natriuretic peptide (ANP) and phosphorylation levels of p44\/42 MAPK without any change in cardiac mass. The cardiac cGMP levels and PKG-mediated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) (Ser239) did not alter in any group. At the highest dose of treatment (100 mg\/kg per day), PKA-mediated phosphorylations of VASP (Ser157) and troponin I (TnI) (Ser23\/24) were enhanced significantly indicating the increase in PKA activation in response to chronic NOS blockage. Alterations in both phosphorylated phospholamban (Ser16\/Thr17) and sarcoplasmic\/endoplasmic Ca<jats:sup>2+<\/jats:sup>-ATPase (SERCA2) levels can increase cytosolic Ca<jats:sup>2+<\/jats:sup> load and impair Ca<jats:sup>2+<\/jats:sup> handling. Our data suggest that the increased PKA activation in response to chronic NOS blockage appears to be responsible for cardiac abnormalities that occur due to prolonged L-NAME treatment. <\/jats:p>","DOI":"10.1139\/cjpp-2018-0388","type":"journal-article","created":{"date-parts":[[2018,11,2]],"date-time":"2018-11-02T21:35:01Z","timestamp":1541194501000},"page":"313-319","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic inhibition of nitric oxide synthase modulates calcium handling in rat heart"],"prefix":"10.1139","volume":"97","author":[{"given":"I\u015f\u0131l","family":"\u00d6zakca","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Turkey."},{"name":"Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Turkey."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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