{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T13:03:25Z","timestamp":1779800605031,"version":"3.53.1"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005297","name":"Uniwersytet Medyczny w Bialymstoku","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pulmonary arterial hypertension (PAH) is a severe multifactorial disease associated with impaired pulmonary hemodynamics, leading to right ventricular (RV) hypertrophy and failure. Induction of inducible nitric oxide synthase (iNOS) and\/or activation of cannabinoid CB\n                      <jats:sub>1<\/jats:sub>\n                      receptor (CB\n                      <jats:sub>1<\/jats:sub>\n                      R) is associated with pro-inflammatory, pro-fibrotic, and pro-hypertrophic effects. Therefore, we tested the effects of chronic simultaneous iNOS\/CB\n                      <jats:sub>1<\/jats:sub>\n                      R blockade in a rat model of monocrotaline-induced pulmonary hypertension (MCT-PH).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Rats were injected with monocrotaline or saline (control) and from day 8 after PH induction they received iNOS inhibitor 1400W, peripheral CB\n                      <jats:sub>1<\/jats:sub>\n                      R antagonist JD5037, their combination or relevant vehicles for 17 days. Invasive and non-invasive hemodynamic assessments, biochemical and histological analyses were conducted. Moreover, the contractions of isolated right ventricular papillary muscles in response to \u03b2-adrenoreceptor agonist were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>1400W improved MCT-impaired rates in rise\/decrease in RV pressure. JD5037 administration reduced MCT-induced increase in mean pulmonary artery pressure (mPAP), RV wall thickness, and improved pulmonary artery Doppler parameters. 1400W + JD5037 combined therapy exerted the most beneficial effects. It reduced RV systolic pressure, mPAP, attenuated RV hypertrophy, with improvement of RV function and blood oxygen saturation. Moreover, it showed anti-inflammatory and anti-remodeling properties. However, no effects on lung hypertrophy, electrocardiographic parameters, and positive inotropic effect of \u03b2-adrenoreceptor agonist were revealed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our results demonstrated that dual pharmacological iNOS\/CB\n                      <jats:sub>1<\/jats:sub>\n                      R blockade is more beneficial in MCT-induced PH amelioration than modulation of any single target alone. Therefore, it could be seen as a promising novel PAH treatment strategy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1831802","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T12:10:21Z","timestamp":1779797421000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic simultaneous inducible nitric oxide synthase (iNOS) and peripheral cannabinoid CB1 receptors blockade ameliorates pulmonary hypertension in monocrotaline-induced rat model"],"prefix":"10.3389","volume":"17","author":[{"given":"Piotr","family":"Ryszkiewicz","sequence":"first","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Medical University of Bia\u0142ystok","place":["Bia\u0142ystok, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patryk","family":"Remiszewski","sequence":"additional","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Medical University of Bia\u0142ystok","place":["Bia\u0142ystok, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"P\u0119dzi\u0144ska-Betiuk","sequence":"additional","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Medical University of Bia\u0142ystok","place":["Bia\u0142ystok, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Mi\u0144czuk","sequence":"additional","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Medical University of Bia\u0142ystok","place":["Bia\u0142ystok, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Baranowska-Kuczko","sequence":"additional","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Medical University of Bia\u0142ystok","place":["Bia\u0142ystok, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanta","family":"Weresa","sequence":"additional","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Medical University of Bia\u0142ystok","place":["Bia\u0142ystok, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Malinowska","sequence":"additional","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Medical University of Bia\u0142ystok","place":["Bia\u0142ystok, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e2207454","DOI":"10.1002\/advs.202207454","article-title":"An integrative multiomics framework for identification of therapeutic targets in pulmonary fibrosis","volume":"10","author":"Arif","year":"2023","journal-title":"Adv. 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