{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:25:58Z","timestamp":1787160358636,"version":"build-2736575974"},"reference-count":60,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A high salt intake exacerbates insulin resistance, evoking hypertension due to systemic perivascular inflammation, oxidative-nitrosative stress and endothelial dysfunction. Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARBs) have been shown to abolish inflammation and redox stress but only partially restore endothelial function in mesenteric vessels. We investigated whether sympatho-adrenal overactivation evokes coronary vascular dysfunction when a high salt intake is combined with insulin resistance in male Goto\u2013Kakizaki (GK) and Wistar rats treated with two different classes of \u03b2-blocker or vehicle, utilising synchrotron-based microangiography in vivo. Further, we examined if chronic carvedilol (CAR) treatment preserves nitric oxide (NO)-mediated coronary dilation more than metoprolol (MET). A high salt diet (6% NaCl w\/w) exacerbated coronary microvessel endothelial dysfunction and NO-resistance in vehicle-treated GK rats while Wistar rats showed modest impairment. Microvascular dysfunction was associated with elevated expression of myocardial endothelin, inducible NO synthase (NOS) protein and 3-nitrotyrosine (3-NT). Both CAR and MET reduced basal coronary perfusion but restored microvessel endothelium-dependent and -independent dilation indicating a role for sympatho-adrenal overactivation in vehicle-treated rats. While MET treatment reduced myocardial nitrates, only MET treatment completely restored microvessel dilation to dobutamine (DOB) stimulation in the absence of NO and prostanoids (combined inhibition), indicating that MET restored the coronary flow reserve attributable to endothelium-derived hyperpolarisation (EDH). In conclusion, sympatho-adrenal overactivation caused by high salt intake and insulin resistance evoked coronary microvessel endothelial dysfunction and diminished NO sensitivity, which were restored by MET and CAR treatment in spite of ongoing inflammation and oxidative-nitrosative stress presumably caused by uninhibited renin\u2013angiotensin\u2013aldosterone system (RAAS) overactivation.<\/jats:p>","DOI":"10.1042\/cs20201441","type":"journal-article","created":{"date-parts":[[2021,1,23]],"date-time":"2021-01-23T13:21:12Z","timestamp":1611408072000},"page":"327-346","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["\u03b2-blockade prevents coronary macro- and microvascular dysfunction induced by a high salt diet and insulin resistance in the Goto\u2013Kakizaki rat"],"prefix":"10.1042","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3318-5406","authenticated-orcid":false,"given":"James\u00a0T.","family":"Pearson","sequence":"first","affiliation":[{"name":"Departments of Cardiac Physiology and Advanced Medical Research in Pulmonary Hypertension, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan"},{"name":"Monash Biomedicine Institute and Department of Physiology, Monash University, Melbourne, Australia"},{"name":"Monash Biomedical Imaging Facility, Monash University, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamish\u00a0P.","family":"Thambyah","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Institute and Department of Physiology, Monash University, Melbourne, Australia"},{"name":"St Vincent\u2019s Hospital, University of Melbourne, Melbourne, 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Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer\u00a0P.","family":"Ngo","sequence":"additional","affiliation":[{"name":"Departments of Cardiac Physiology and Advanced Medical Research in Pulmonary Hypertension, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie\u00a0P.C.","family":"Ow","sequence":"additional","affiliation":[{"name":"Departments of Cardiac Physiology and Advanced Medical Research in Pulmonary Hypertension, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Sonobe","sequence":"additional","affiliation":[{"name":"Departments of Cardiac Physiology and Advanced Medical Research in Pulmonary Hypertension, National Cerebral and Cardiovascular Center Research Institute, Suita, 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