{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:11:29Z","timestamp":1789884689252,"version":"4.0.1"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,28]],"date-time":"2018-12-28T00:00:00Z","timestamp":1545955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP16K08563"],"award-info":[{"award-number":["JP16K08563"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perivascular adipose tissue (PVAT) can regulate vascular tone. In mesenteric arteries of SHRSP.Z-Leprfa\/IzmDmcr rats (SHRSP.ZF) with metabolic syndrome, vascular dysfunction is compensated by PVAT-dependent mechanisms that disappear with increasing age. In this study, we investigated the mechanisms of the age-related changes and responsible factor(s) involved in the enhancing effects of mesenteric arterial PVAT in SHRSP.ZF. Acetylcholine- and sodium nitroprusside-induced relaxations of isolated arteries were greater with PVAT than without PVAT at 17 and 20 weeks of age (wks), and as expected, this enhancement by the presence of PVAT disappeared at 23 wks. PVAT mRNA levels of angiotensin II type 1 (AT1) receptor-associated protein was less and AT1 receptor was unchanged at 23 wks when compared to 20 wks. At 20 wks, the enhanced acetylcholine-induced relaxation by the presence of PVAT was inhibited by N-acetyl-l-cysteine (NAC). Acetylcholine-induced relaxation of arteries without PVAT was increased in the presence of exogenously added apelin. PVAT mRNA level of apelin was higher in SHRSP.ZF than in control Wistar-Kyoto rats, and the level was decreased with aging. These results suggest that AT1 receptor activation in PVAT, and changes in the regulation of apelin and a NAC-sensitive factor are related to the age-dependent deterioration of the vasodilation enhancing effects of mesenteric arterial PVAT in SHRSP.ZF.<\/jats:p>","DOI":"10.3390\/ijms20010106","type":"journal-article","created":{"date-parts":[[2018,12,28]],"date-time":"2018-12-28T11:52:42Z","timestamp":1545997962000},"page":"106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Perivascular Adipose Tissue-Enhanced Vasodilation in Metabolic Syndrome Rats by Apelin and N-Acetyl\u2013l-Cysteine-Sensitive Factor(s)"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2044-5552","authenticated-orcid":false,"given":"Satomi","family":"Kagota","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women\u2019s University, Nishinomiya 663 8184, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Maruyama-Fumoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women\u2019s University, Nishinomiya 663 8184, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women\u2019s University, Nishinomiya 663 8184, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Shimari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women\u2019s University, Nishinomiya 663 8184, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiori","family":"Koyanagi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women\u2019s University, Nishinomiya 663 8184, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayoi","family":"Shiokawa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women\u2019s University, Nishinomiya 663 8184, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0302-3884","authenticated-orcid":false,"given":"John J.","family":"McGuire","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Schulich School of Medicine &amp; Dentistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumasa","family":"Shinozuka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women\u2019s University, Nishinomiya 663 8184, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s11906-016-0692-z","article-title":"A clinical perspective: Contribution of dysfunctional perivascular adipose tissue (PVAT) to cardiovascular risk","volume":"18","author":"Lian","year":"2016","journal-title":"Curr. 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