{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:14:24Z","timestamp":1770743664528,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,2]],"date-time":"2021-05-02T00:00:00Z","timestamp":1619913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Bia\u0142ystok","award":["SUB\/2\/DN\/20\/006\/2213"],"award-info":[{"award-number":["SUB\/2\/DN\/20\/006\/2213"]}]},{"name":"Medical University of Bia\u0142ystok","award":["SUB\/2\/DN\/20\/002\/2213"],"award-info":[{"award-number":["SUB\/2\/DN\/20\/002\/2213"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Our study aimed to examine the effects of hypertension and the chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on vascular function and the endocannabinoid system in spontaneously hypertensive rats (SHR). Functional studies were performed on small mesenteric G3 arteries (sMA) and aortas isolated from SHR and normotensive Wistar Kyoto rats (WKY) treated with URB597 (1 mg\/kg; twice daily for 14 days). In the aortas and sMA of SHR, endocannabinoid levels and cannabinoid CB1 receptor (CB1R) expression were elevated. The CB1R antagonist AM251 diminished the methanandamide-evoked relaxation only in the sMA of SHR and enhanced the vasoconstriction induced by phenylephrine and the thromboxane analog U46619 in sMA in SHR and WKY. In the sMA of SHR, URB597 elevated anandamide levels, improved the endothelium-dependent vasorelaxation to acetylcholine, and in the presence of AM251 reduced the vasoconstriction to phenylephrine and enhanced the vasodilatation to methanandamide, and tended to reduce hypertrophy. In the aortas, URB597 elevated endocannabinoid levels improved the endothelium-dependent vasorelaxation to acetylcholine and decreased CB1R expression. Our study showed that hypertension and chronic administration of URB597 caused local, resistance artery-specific beneficial alterations in the vascular endocannabinoid system, which may bring further advantages for therapeutic application of pharmacological inhibition of FAAH.<\/jats:p>","DOI":"10.3390\/ijms22094833","type":"journal-article","created":{"date-parts":[[2021,5,2]],"date-time":"2021-05-02T08:05:21Z","timestamp":1619942721000},"page":"4833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Beneficial Changes in Rat Vascular Endocannabinoid System in Primary Hypertension and under Treatment with Chronic Inhibition of Fatty Acid Amide Hydrolase by URB597"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7238-2656","authenticated-orcid":false,"given":"Marta","family":"Baranowska-Kuczko","sequence":"first","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Medical University of Bia\u0142ystok, ul. Mickiewicza 2A, 15-222 Bia\u0142ystok, Poland"},{"name":"Department of Clinical Pharmacy, Medical University of Bia\u0142ystok, ul. Mickiewicza 2A, 15-222 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2105-3350","authenticated-orcid":false,"given":"Hanna","family":"Koz\u0142owska","sequence":"additional","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Medical University of Bia\u0142ystok, ul. Mickiewicza 2A, 15-222 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Kloza","sequence":"additional","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Medical University of Bia\u0142ystok, ul. Mickiewicza 2A, 15-222 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3507-4686","authenticated-orcid":false,"given":"Ewa","family":"Harasim-Symbor","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical University of Bia\u0142ystok, ul. Mickiewicza 2C, 15-222 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9101-5125","authenticated-orcid":false,"given":"Micha\u0142","family":"Biernacki","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Medical University of Bia\u0142ystok, ul. Mickiewicza 2D, 15-222 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2954-942X","authenticated-orcid":false,"given":"Irena","family":"Kasacka","sequence":"additional","affiliation":[{"name":"Department of Histology and Cytophysiology, Medical University of Bia\u0142ystok, ul. Mickiewicza 2C, 15-222 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Malinowska","sequence":"additional","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Medical University of Bia\u0142ystok, ul. Mickiewicza 2A, 15-222 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1111\/bph.14168","article-title":"Cannabinoids in arterial, pulmonary and portal hypertension\u2014Mechanisms of action and potential therapeutic significance","volume":"176","author":"Malinowska","year":"2019","journal-title":"Br. J. 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