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The hugely varying doses used clinically have contributed to this confusion, with high\u2010dose aspirin still commonly used due to concerns about the efficacy of low\u2010dose aspirin. Because prostaglandins have been shown to both promote and inhibit T\u2010cell activation, we also explored the immunomodulatory properties of aspirin in hypertension. Although the common preclinical high dose of 100 mg\/kg\/d improved vascular dysfunction and cardiac hypertrophy, this effect was accompanied by indices of elevated adaptive immunity, renal T\u2010cell infiltration, renal fibrosis, and BP elevation in stroke\u2010prone spontaneously hypertensive rats and in angiotensin II\u2010induced hypertensive mice. The cardioprotective effects of aspirin were conserved with a lower dose (10 mg\/kg\/d) while circumventing heightened adaptive immunity and elevated BP. We also show that low\u2010dose aspirin improves renal fibrosis. Differential inhibition of the COX\u20102 isoform may underlie the disparate effects of the 2 doses. Our results demonstrate the efficacy of low\u2010dose aspirin in treating a vast array of cardiovascular parameters and suggest modulation of adaptive immunity as a novel mechanism underlying adverse cardiovascular profiles associated with COX\u20102 inhibitors. Clinical studies should identify the dose of aspirin that achieves maximal cardioprotection with a new awareness that higher doses of aspirin could trigger undesired autoimmunity in hypertensive individuals. This work also warrants an evaluation of high\u2010dose aspirin and COX\u20102 inhibitor therapy in sufferers of inflammatory conditions who are already at increased risk for cardiovascular disease.\u2014Khan, S. I., Shihata, W. A., Andrews, K. L., Lee, M. K. S., Moore, X.\u2010L., Jefferis, A.\u2010M., Vinh, A., Gaspari, T., Dragoljevic, D., Jennings, G. L., Murphy, A. J., Chin\u2010Dusting, J. P. F. Effects of high\u2010 and low\u2010dose aspirin on adaptive immunity and hypertension in the stroke\u2010prone spontaneously hypertensive rat. FASEB J. 33, 1510\u20131521 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201701498rr","type":"journal-article","created":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T12:11:19Z","timestamp":1535544679000},"page":"1510-1521","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effects of high\u2010 and low\u2010dose aspirin on adaptive immunity and hypertension in the stroke\u2010prone spontaneously hypertensive rat"],"prefix":"10.1096","volume":"33","author":[{"given":"Shanzana I.","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Pharmacology Biomedicine Discovery Institute Monash University  Clayton Victoria Australia"},{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"},{"name":"Department of Medicine Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waled A.","family":"Shihata","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Biomedicine Discovery Institute Monash University  Clayton Victoria Australia"},{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"},{"name":"Department of Medicine Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Biomedicine Discovery Institute Monash University  Clayton Victoria Australia"},{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man K. 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